Special Issue "MicroRNA-Associated Cancer Metastasis"

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (31 January 2019)

Special Issue Editor

Guest Editor
Dr. Mitsuhiko Osaki

Division of Pathological Biochemistry, Department of Biomedical Sciences, Faculty of Medicine, Tottori University 86, Nishi-cho, Yonago, Tottori, 683-8503, Japan
Website | E-Mail
Interests: microRNA, cancer metastasis, exosome, molecular pathology, tumor environment

Special Issue Information

Dear Colleagues,

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression, mainly at the post-transcriptional level, by interfering with the translation of one or more target mRNAs. Numerous of studies have reported that miRNAs play important physiological roles, and dysregulation of miRNAs contributes to both tumor development and metastasis. Metastasis still remains the cause of over 90% of cancer deaths, even though the pathogenesis of metastasis has been investigated for more than 150 years. Recently, there have been reports that secreted miRNAs packaged into extracellular vesicles including exosomes contribute to forming a pre-metastatic niche and promote metastasis. Thus, miRNA represents a new class of therapeutics for cancer treatment through inhibition or replacement of dysregulated miRNAs. However, the clinical applicability of miRNA-based therapies is severely limited by the lack of effective delivery systems. It is also important to develop delivery systems for miRNA that target lesions. This Special Issue focuses on understanding the pathological roles of miRNAs in cancer metastasis and on the potential of miRNA-based therapies for the prevention of metastasis, including miRNA delivery systems.

Dr. Mitsuhiko Osaki
Guest Editor

Manuscript Submission Information

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Keywords

  • miRNA
  • metastasis
  • exosome
  • miRNA-delivery system
  • metastasis prevention

Published Papers (14 papers)

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Research

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Open AccessArticle Differential MicroRNA Landscape Triggered by Estrogens in Cancer Associated Fibroblasts (CAFs) of Primary and Metastatic Breast Tumors
Cancers 2019, 11(3), 412; https://doi.org/10.3390/cancers11030412
Received: 25 January 2019 / Revised: 14 March 2019 / Accepted: 20 March 2019 / Published: 23 March 2019
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Abstract
Cancer associated fibroblasts (CAFs) play a main role in breast cancer progression and metastasis. Estrogens modulate in breast CAFs the expression of microRNAs (miRNAs) that are involved in the development of many tumors. In order to provide novel insights on the regulation of [...] Read more.
Cancer associated fibroblasts (CAFs) play a main role in breast cancer progression and metastasis. Estrogens modulate in breast CAFs the expression of microRNAs (miRNAs) that are involved in the development of many tumors. In order to provide novel insights on the regulation of miRNAs by estrogens in breast cancer, we analyzed the expression of 754 miRNAs in CAFs obtained from primary mammary tumors and CAFs derived from a cutaneous breast cancer metastasis. Using the TaqMan™ Human MicroRNA Array, we found that 17β-estradiol (E2) modulates numerous peculiar and common miRNAs in CAFs derived from primary and the metastatic malignancies. In particular, we assessed that E2 modulates 133 miRNAs (41 up and 92 downregulated) in CAFs derived from primary breast tumors, whereas E2 modulates 415 miRNAs (399 up and 16 downregulated) in CAFs derived from a cutaneous metastasis of breast carcinoma. Therefore, a number of miRNAs three times higher in metastatic CAFs with respect to primary breast CAFs was found modulated by E2. Our findings shed new light on the cumulative regulation of miRNAs by E2 in the main players of the tumor microenvironment as CAFs. Moreover, our data may be taken into consideration that is useful toward innovative prognostic and therapeutic approaches in breast cancer progression. Full article
(This article belongs to the Special Issue MicroRNA-Associated Cancer Metastasis)
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Open AccessArticle Gene Regulation by Antitumor miR-204-5p in Pancreatic Ductal Adenocarcinoma: The Clinical Significance of Direct RACGAP1 Regulation
Cancers 2019, 11(3), 327; https://doi.org/10.3390/cancers11030327
Received: 15 January 2019 / Revised: 3 March 2019 / Accepted: 4 March 2019 / Published: 7 March 2019
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Abstract
Previously, we established a microRNA (miRNA) expression signature in pancreatic ductal adenocarcinoma (PDAC) tissues using RNA sequencing and found significantly reduced expression of miR-204-5p. Here, we aimed to investigate the functional significance of miR-204-5p and to identify miR-204-5p target genes involved in [...] Read more.
Previously, we established a microRNA (miRNA) expression signature in pancreatic ductal adenocarcinoma (PDAC) tissues using RNA sequencing and found significantly reduced expression of miR-204-5p. Here, we aimed to investigate the functional significance of miR-204-5p and to identify miR-204-5p target genes involved in PDAC pathogenesis. Cancer cell migration and invasion were significantly inhibited by ectopic expression of miR-204-5p in PDAC cells. Comprehensive gene expression analyses and in silico database searches revealed 25 putative targets regulated by miR-204-5p in PDAC cells. Among these target genes, high expression levels of RACGAP1, DHRS9, AP1S3, FOXC1, PRP11, RHBDL2 and MUC4 were significant predictors of a poor prognosis of patients with PDAC. In this study, we focused on RACGAP1 (Rac guanosine triphosphatase-activating protein 1) because its expression was most significantly predictive of PDAC pathogenesis (overall survival rate: p = 0.0000548; disease-free survival rate: p = 0.0014). Overexpression of RACGAP1 was detected in PDAC clinical specimens, and its expression enhanced the migration and invasion of PDAC cells. Moreover, downstream genes affected by RACGAP1 (e.g., MMP28, CEP55, CDK1, ANLN and S100A14) are involved in PDAC pathogenesis. Our strategy to identify antitumor miRNAs and their target genes will help elucidate the molecular pathogenesis of PDAC. Full article
(This article belongs to the Special Issue MicroRNA-Associated Cancer Metastasis)
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Open AccessArticle Regulation of KIF2A by Antitumor miR-451a Inhibits Cancer Cell Aggressiveness Features in Lung Squamous Cell Carcinoma
Cancers 2019, 11(2), 258; https://doi.org/10.3390/cancers11020258
Received: 27 January 2019 / Revised: 18 February 2019 / Accepted: 18 February 2019 / Published: 22 February 2019
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Abstract
In the human genome, miR-451a is encoded close to the miR-144 on chromosome region 17q11.2. Our previous study showed that both strands of pre-miR-144 acted as antitumor miRNAs and were involved in lung squamous cell carcinoma (LUSQ) pathogenesis. Here, we aimed to [...] Read more.
In the human genome, miR-451a is encoded close to the miR-144 on chromosome region 17q11.2. Our previous study showed that both strands of pre-miR-144 acted as antitumor miRNAs and were involved in lung squamous cell carcinoma (LUSQ) pathogenesis. Here, we aimed to investigate the functional significance of miR-451a and to identify its targeting of oncogenic genes in LUSQ cells. Downregulation of miR-451a was confirmed in LUSQ clinical specimens, and low expression of miR-451a was significantly associated with poor prognosis of LUSQ patients (overall survival: p = 0.035, disease-free survival: p = 0.029). Additionally, we showed that ectopic expression of miR-451a significantly blocked cancer cell aggressiveness. In total, 15 putative oncogenic genes were shown to be regulated by miR-451a in LUSQ cells. Among these targets, high kinesin family member 2A (KIF2A) expression was significantly associated with poor prognosis (overall survival: p = 0.043, disease-free survival: p = 0.028). Multivariate analysis showed that KIF2A expression was an independent prognostic factor in patients with LUSQ (hazard ratio = 1.493, p = 0.034). Aberrant KIF2A expression promoted the malignant transformation of this disease. Analytic strategies based on antitumor miRNAs and their target oncogenes are effective tools for identification of novel molecular pathogenesis of LUSQ. Full article
(This article belongs to the Special Issue MicroRNA-Associated Cancer Metastasis)
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Open AccessArticle Metformin Treatment Suppresses Melanoma Cell Growth and Motility Through Modulation of microRNA Expression
Cancers 2019, 11(2), 209; https://doi.org/10.3390/cancers11020209
Received: 15 January 2019 / Revised: 2 February 2019 / Accepted: 5 February 2019 / Published: 11 February 2019
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Abstract
Melanoma is a highly aggressive cancer with high mortality in advanced stages.
Metformin is an oral biguanide drug used for diabetes and has demonstrated positive effects on
cancer prevention and treatment. Herein, we found that metformin significantly suppressed
melanoma cancer cell motility and [...] Read more.
Melanoma is a highly aggressive cancer with high mortality in advanced stages.
Metformin is an oral biguanide drug used for diabetes and has demonstrated positive effects on
cancer prevention and treatment. Herein, we found that metformin significantly suppressed
melanoma cancer cell motility and growth through inducing cell cycle arrest at the G2/M phase and
promoting cell apoptosis. Using the next-generation sequencing approach, we identified three
upregulated microRNAs (miRNA; miR-192-5p, miR-584-3p, and miR-1246) in melanoma cells
treated with metformin. Among these, we examined the roles of miR-192-5p and miR-584-3p and
discovered that they significantly suppressed melanoma cell motility. Furthermore, they inhibited
melanoma cell growth through destroying cell cycle progression and inducing cell apoptosis. Using
microarray and bioinformatics approaches for identifying putative target genes, Epidermal growth
factor (EGF) containing fibulin-like extracellular matrix protein 1 (EFEMP1) gene for miR-192-5p
and an isoform of the secretory carrier membrane proteins (SCAMP3) gene for miR-584-3p could be
silenced through targeting their 3′UTR region directly. EFEMP1 and SCAMP3 knockdown
significantly suppressed melanoma cell growth, but only EFEMP1 knockdown inhibited its motility
abilities. Our findings indicated that miR-192-5p and miR-584-3p might contribute to metformininduced
growth and motility suppression in melanoma cells through silencing their target genes
EFEMP1 and SCAMP3. Full article
(This article belongs to the Special Issue MicroRNA-Associated Cancer Metastasis)
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Open AccessArticle NACC1, as a Target of MicroRNA-331-3p, Regulates Cell Proliferation in Urothelial Carcinoma Cells
Cancers 2018, 10(10), 347; https://doi.org/10.3390/cancers10100347
Received: 19 August 2018 / Revised: 12 September 2018 / Accepted: 20 September 2018 / Published: 21 September 2018
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Abstract
The nucleus accumbens-associated protein 1 (NACC1) is a transcription factor constitutively expressed in the urothelium, where it regulates cell growth, senescence, autophagy, and epithelial-mesenchymal transition. microRNA (miRNA) constitutes a class of small non-coding RNAs which are involved in cell proliferation, differentiation, and progression [...] Read more.
The nucleus accumbens-associated protein 1 (NACC1) is a transcription factor constitutively expressed in the urothelium, where it regulates cell growth, senescence, autophagy, and epithelial-mesenchymal transition. microRNA (miRNA) constitutes a class of small non-coding RNAs which are involved in cell proliferation, differentiation, and progression of tumors. miRNAs and their target molecules are utilized for molecular diagnosis of urothelial carcinoma. NACC1 is one of several putative target molecules of miR-331-3p, and is associated with cell proliferation in cancers such as prostate and cervical cancer. Functional experiments involving miR-331-3p and its target molecule NACC1 were conducted using the urothelial carcinoma (UC) cell lines, T24, UMUC6, and KU7. Furthermore, quantitative reverse transcription polymerase chain reaction and immunostaining were performed to evaluate the expression of NACC1 in UC derived from transurethral resection of bladder tumor (TUR-Bt) specimens. The methane thiosulfonate (MTS) assay revealed that cell proliferation was significantly reduced after transient transfection of miR-331-3p precursor and/or NACC1 siRNA in UC cells. Cell senescence via cell cycle arrest at the G1 phase was induced by NACC1 inhibition. On the other hand, suppression of NACC1 induced cell migration and invasion abilities. Immunohistochemical analysis of TUR-Bt specimens revealed that over 70% of UC cells presented strongly positive results for NACC1. In contrast, normal urothelial cells were weakly positive for NACC1. It was also found that NACC1 expression was lower in invasive UC cells than in non-invasive UC cells. Loss of NACC1 induced vessel invasion in invasive UC tissues. The present results indicate that NACC1 regulated by miR-331-3p contributes to cell proliferation, and is involved in cell migration and invasion. This suggests that NACC1 can serve as a potential target molecule for the prediction and prognosis of UC, and can contribute to effective treatment strategies. Full article
(This article belongs to the Special Issue MicroRNA-Associated Cancer Metastasis)
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Open AccessArticle Clinical Impact of Epithelial-to-Mesenchymal Transition Regulating MicroRNAs in Pancreatic Ductal Adenocarcinoma
Cancers 2018, 10(9), 328; https://doi.org/10.3390/cancers10090328
Received: 6 August 2018 / Revised: 30 August 2018 / Accepted: 11 September 2018 / Published: 13 September 2018
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Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive carcinoma entities worldwide with early and rapid dissemination. Recently, we discussed the role of microRNAs as epigenetic regulators of Epithelial-to-Mesenchymal Transition (EMT) in PDAC. In this study, we investigated their value as diagnostic [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive carcinoma entities worldwide with early and rapid dissemination. Recently, we discussed the role of microRNAs as epigenetic regulators of Epithelial-to-Mesenchymal Transition (EMT) in PDAC. In this study, we investigated their value as diagnostic and prognostic markers in tissue and blood samples of 185 patients including PDAC, non-malignant pancreatic disorders, and age-matched healthy controls. Expression of the microRNA-200-family (microRNAs -141, -200a, -200b, -200c, -429) and microRNA-148a was significantly downregulated in tissue of PDAC Union internationale contre le cancer (UICC) Stage II. Correspondingly, stromal PDAC tissue showed strong expression of Fibronectin, Vimentin, and ZEB-1 (Zinc finger E-box-binding homeobox) versus low expression of E-cadherin. Transient transfection of microRNA-200b and microRNA-200c mimics resulted in the downregulation of their key target ZEB-1. Inversely, blood serum analyses of patients with PDAC UICC Stages II, III, and IV showed a significant over-expression of microRNA-200-family members, microRNA-148a, microRNA-10b, and microRNA-34a. Correspondingly, Enzyme-linked Immunosorbent Assay (ELISA) analyses revealed a significant over-expression of soluble E-cadherin in serum samples of PDAC patients versus healthy controls. The best diagnostic accuracy to distinguish between PDAC and non-PDAC in this patient collective could be achieved in tissue by microRNA-148a with an area under the receiver-operating-characteristic (ROC) curve (AUC) of 0.885 and in blood serum by a panel of microRNA-141, -200b, -200c, and CA.19-9 with an AUC of 0.890. Both diagnostic tools outreach the diagnostic performance of the currently most common diagnostic biomarker CA.19-9 (AUC of 0.834). Kaplan Meier survival analysis of this patient collective revealed an improved overall survival in PDAC patients with high expression of tissue-related microRNA-34a, -141, -200b, -200c, and -429. In conclusion, EMT-regulating microRNAs have great potential as liquid and solid biopsy markers in PDAC patients. Their prognostic and therapeutic benefits remain important tasks for future studies. Full article
(This article belongs to the Special Issue MicroRNA-Associated Cancer Metastasis)
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Open AccessArticle Could miRNA Signatures be Useful for Predicting Uterine Sarcoma and Carcinosarcoma Prognosis and Treatment?
Cancers 2018, 10(9), 315; https://doi.org/10.3390/cancers10090315
Received: 21 July 2018 / Revised: 1 September 2018 / Accepted: 4 September 2018 / Published: 6 September 2018
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Abstract
Changes in microRNA (miRNA) expression may lead to cancer development and/or contribute to its progression; however, their role in uterine sarcomas is poorly understood. Uterine sarcomas (US) belong to a rare class of heterogeneous tumors, representing about 1% of all gynecologic neoplasms. This [...] Read more.
Changes in microRNA (miRNA) expression may lead to cancer development and/or contribute to its progression; however, their role in uterine sarcomas is poorly understood. Uterine sarcomas (US) belong to a rare class of heterogeneous tumors, representing about 1% of all gynecologic neoplasms. This study aimed to assess the expression profile of 84 cancer-related miRNAs and to evaluate their correlation with clinical pathological features. Eighty-two formalin-fixed paraffin-embedded (FFPE) samples were selected. In leiomyosarcoma (LMS), there was an association of lower cancer-specific survival (CSS) with the downregulation of miR-125a-5p and miR-10a-5p, and the upregulation of miR-196a-5p and miR-34c-5p. In carcinosarcoma (CS), lower CSS was associated with the upregulation of miR-184, and the downregulation of let-7b-5p and miR-124. In endometrial stromal sarcomas (ESS), the upregulation of miR-373-3p, miR-372-3p, and let-7b-5p, and the down-expression of let-7f-5p, miR-23-3p, and let-7b-5p were associated with lower CSS. Only miR-138-5p upregulation was associated with higher survival rates. miR-335-5p, miR-301a-3p, and miR-210-3p were more highly expressed in patients with tumor metastasis and relapse. miR-138-5p, miR-146b-5p, and miR-218-5p expression were associated with higher disease-free survival (DFS) in treated patients. These miRNAs represent potential prediction markers for prognosis and treatment response in these tumors. Full article
(This article belongs to the Special Issue MicroRNA-Associated Cancer Metastasis)
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Review

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Open AccessReview MicroRNA-Based Diagnosis and Treatment of Metastatic Human Osteosarcoma
Cancers 2019, 11(4), 553; https://doi.org/10.3390/cancers11040553
Received: 2 April 2019 / Revised: 15 April 2019 / Accepted: 16 April 2019 / Published: 18 April 2019
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Abstract
Osteosarcoma is a malignant tumor of the bones that commonly occurs in young individuals. The 5-year survival rate of osteosarcoma patients is 60–70%. Metastasis to the lungs leads to death in 30–40% of osteosarcoma patients. Therefore, the development of effective strategies for early [...] Read more.
Osteosarcoma is a malignant tumor of the bones that commonly occurs in young individuals. The 5-year survival rate of osteosarcoma patients is 60–70%. Metastasis to the lungs leads to death in 30–40% of osteosarcoma patients. Therefore, the development of effective strategies for early detection and treatment of this disease are important to improve the survival of osteosarcoma patients. However, metastatic markers for osteosarcoma and molecules that might be targeted for the treatment of metastatic osteosarcoma have not been identified yet. Therefore, the mechanism of metastasis to the lungs needs to be explored from a novel viewpoint. Recently, the aberrant expression of microRNAs (miRNAs) has been reported to be involved in the carcinogenesis and cancer progression of many cancers. Furthermore, miRNAs in the blood have been reported to show an aberrant expression unique to several cancers. Therefore, miRNAs are gaining attention as potential diagnostic markers for cancers. On the other hand, normalizing the dysregulated expression of miRNAs in cancer cells has been shown to alter the phenotype of cancer cells, and thus treatment strategies targeting miRNAs are also being considered. This review summarizes the abnormality of miRNA expression associated with the metastasis of osteosarcoma and describes the present situation and issues regarding the early diagnosis and development of treatment strategies for metastatic osteosarcoma based on the current understanding of this disease. Full article
(This article belongs to the Special Issue MicroRNA-Associated Cancer Metastasis)
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Open AccessReview An Insight into the Roles of MicroRNAs and Exosomes in Sarcoma
Cancers 2019, 11(3), 428; https://doi.org/10.3390/cancers11030428
Received: 14 February 2019 / Revised: 20 March 2019 / Accepted: 21 March 2019 / Published: 26 March 2019
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Abstract
Sarcomas are rare solid tumors, but at least one-third of patients with sarcoma die from tumor-related disease. MicroRNA (miRNA) is a noncoding RNA that regulates gene expression in all cells and plays a key role in the progression of cancers. Recently, it was [...] Read more.
Sarcomas are rare solid tumors, but at least one-third of patients with sarcoma die from tumor-related disease. MicroRNA (miRNA) is a noncoding RNA that regulates gene expression in all cells and plays a key role in the progression of cancers. Recently, it was identified that miRNAs are transferred between cells by enclosure in extracellular vesicles, especially exosomes. The exosome is a 100 nm-sized membraned vesicle that is secreted by many kinds of cells and contains miRNA, mRNA, DNA, and proteins. Cancer uses exosomes to influence not only the tumor microenvironment but also the distant organ to create a premetastatic niche. The progression of sarcoma is also regulated by miRNAs and exosomes. These miRNAs and exosomes can be targeted as biomarkers and treatments. In this review, we summarize the studies of miRNA and exosomes in sarcoma. Full article
(This article belongs to the Special Issue MicroRNA-Associated Cancer Metastasis)
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Open AccessReview The Role of MicroRNAs in Recurrence and Metastasis of Head and Neck Squamous Cell Carcinoma
Cancers 2019, 11(3), 395; https://doi.org/10.3390/cancers11030395
Received: 27 February 2019 / Revised: 18 March 2019 / Accepted: 19 March 2019 / Published: 21 March 2019
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Abstract
Head and neck squamous cell carcinoma (HNSCC) affects 650,000 people worldwide and has a dismal 50% 5-year survival rate. Recurrence and metastasis are believed the two most important factors causing this high mortality. Understanding the biological process and the underlying mechanisms of recurrence [...] Read more.
Head and neck squamous cell carcinoma (HNSCC) affects 650,000 people worldwide and has a dismal 50% 5-year survival rate. Recurrence and metastasis are believed the two most important factors causing this high mortality. Understanding the biological process and the underlying mechanisms of recurrence and metastasis is critical to develop novel and effective treatment, which is expected to improve patients’ survival of HNSCC. MicroRNAs are small, non-coding nucleotides that regulate gene expression at the transcriptional and post-transcriptional level. Oncogenic and tumor-suppressive microRNAs have shown to regulate nearly every step of recurrence and metastasis, ranging from migration and invasion, epithelial-mesenchymal transition (EMT), anoikis, to gain of cancer stem cell property. This review encompasses an overview of microRNAs involved in these processes. The recent advances of utilizing microRNA as biomarkers and targets for treatment, particularly on controlling recurrence and metastasis are also reviewed. Full article
(This article belongs to the Special Issue MicroRNA-Associated Cancer Metastasis)
Open AccessReview Role of miRNAs in Melanoma Metastasis
Cancers 2019, 11(3), 326; https://doi.org/10.3390/cancers11030326
Received: 31 January 2019 / Revised: 28 February 2019 / Accepted: 2 March 2019 / Published: 7 March 2019
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Abstract
Tumour metastasis is a multistep process. Melanoma is a highly aggressive cancer and metastasis accounts for the majority of patient deaths. microRNAs (miRNAs) are non-coding RNAs that affect the expression of their target genes. When aberrantly expressed they contribute to the development of [...] Read more.
Tumour metastasis is a multistep process. Melanoma is a highly aggressive cancer and metastasis accounts for the majority of patient deaths. microRNAs (miRNAs) are non-coding RNAs that affect the expression of their target genes. When aberrantly expressed they contribute to the development of melanoma. While miRNAs can act locally in the cell where they are synthesized, they can also influence the phenotype of neighboring melanoma cells or execute their function in the direct tumour microenvironment by modulating ECM (extracellular matrix) and the activity of fibroblasts, endothelial cells, and immune cells. miRNAs are involved in all stages of melanoma metastasis, including intravasation into the lumina of vessels, survival during circulation in cardiovascular or lymphatic systems, extravasation, and formation of the pre-metastatic niche in distant organs. miRNAs contribute to metabolic alterations that provide a selective advantage during melanoma progression. They play an important role in the development of drug resistance, including resistance to targeted therapies and immunotherapies. Distinct profiles of miRNA expression are detected at each step of melanoma development. Since miRNAs can be detected in liquid biopsies, they are considered biomarkers of early disease stages or response to treatment. This review summarizes recent findings regarding the role of miRNAs in melanoma metastasis. Full article
(This article belongs to the Special Issue MicroRNA-Associated Cancer Metastasis)
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Open AccessReview MicroRNA in Lung Cancer Metastasis
Cancers 2019, 11(2), 265; https://doi.org/10.3390/cancers11020265
Received: 31 January 2019 / Revised: 17 February 2019 / Accepted: 18 February 2019 / Published: 23 February 2019
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Abstract
Tumor metastasis is a hallmark of cancer, with distant metastasis frequently developing in lung cancer, even at initial diagnosis, resulting in poor prognosis and high mortality. However, available biomarkers cannot reliably predict cancer spreading sites. The metastatic cascade involves highly complicated processes including [...] Read more.
Tumor metastasis is a hallmark of cancer, with distant metastasis frequently developing in lung cancer, even at initial diagnosis, resulting in poor prognosis and high mortality. However, available biomarkers cannot reliably predict cancer spreading sites. The metastatic cascade involves highly complicated processes including invasion, migration, angiogenesis, and epithelial-to-mesenchymal transition that are tightly controlled by various genetic expression modalities along with interaction between cancer cells and the extracellular matrix. In particular, microRNAs (miRNAs), a group of small non-coding RNAs, can influence the transcriptional and post-transcriptional processes, with dysregulation of miRNA expression contributing to the regulation of cancer metastasis. Nevertheless, although miRNA-targeted therapy is widely studied in vitro and in vivo, this strategy currently affords limited feasibility and a few miRNA-targeted therapies for lung cancer have entered into clinical trials to date. Advances in understanding the molecular mechanism of metastasis will thus provide additional potential targets for lung cancer treatment. This review discusses the current research related to the role of miRNAs in lung cancer invasion and metastasis, with a particular focus on the different metastatic lesions and potential miRNA-targeted treatments for lung cancer with the expectation that further exploration of miRNA-targeted therapy may establish a new spectrum of lung cancer treatments. Full article
(This article belongs to the Special Issue MicroRNA-Associated Cancer Metastasis)
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Open AccessReview The Role of MicroRNAs in the Metastatic Process of High-Risk HPV-Induced Cancers
Cancers 2018, 10(12), 493; https://doi.org/10.3390/cancers10120493
Received: 9 November 2018 / Revised: 30 November 2018 / Accepted: 3 December 2018 / Published: 5 December 2018
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Abstract
High-risk human papillomavirus (HPV)-driven cancers represent a major health concern worldwide. Despite the constant effort to develop and promote vaccination against HPVs, there is still a high percentage of non-vaccinated population. Furthermore, secondary prevention programs are not ubiquitous worldwide and not widely followed. [...] Read more.
High-risk human papillomavirus (HPV)-driven cancers represent a major health concern worldwide. Despite the constant effort to develop and promote vaccination against HPVs, there is still a high percentage of non-vaccinated population. Furthermore, secondary prevention programs are not ubiquitous worldwide and not widely followed. Metastatic disease is the cause of the great majority of cancer-associated deaths, making it essential to determine its underlying mechanisms and to identify actionable anti-metastatic targets. Within certain types of cancer (e.g., head and neck), HPV-positive tumors show different dissemination patterns when compared with their HPV-negative counterparts, implicating HPV-related factors in the metastatic process. Among the many groups of biomolecules dysregulated by HPV, microRNAs have recently emerged as key regulators of carcinogenesis, able to control complex processes like cancer metastization. In this review, we present recent data on the role of microRNAs in the metastization of HPV-related cancers and on their possible clinical relevance as biomarkers of metastatic disease and/or as therapeutic targets. Full article
(This article belongs to the Special Issue MicroRNA-Associated Cancer Metastasis)
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Open AccessReview Involving the microRNA Targetome in Esophageal-Cancer Development and Behavior
Cancers 2018, 10(10), 381; https://doi.org/10.3390/cancers10100381
Received: 30 August 2018 / Revised: 9 October 2018 / Accepted: 10 October 2018 / Published: 12 October 2018
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Abstract
Esophageal cancer (EC) is the eighth most common and sixth leading cause of cancer-related mortality in the world. Despite breakthroughs in EC diagnosis and treatment, patients with complete pathologic response after being submitted to chemoradiotherapy are still submitted to surgery, despite its high [...] Read more.
Esophageal cancer (EC) is the eighth most common and sixth leading cause of cancer-related mortality in the world. Despite breakthroughs in EC diagnosis and treatment, patients with complete pathologic response after being submitted to chemoradiotherapy are still submitted to surgery, despite its high morbidity. Single-nucleotide polymorphisms (SNPs) in miRNA, miRNA-binding sites, and in its biogenesis pathway genes can alter miRNA expression patterns, thereby influencing cancer risk and prognosis. In this review, we systematized the information available regarding the impact of these miR-SNPs in EC development and prognosis. We found 34 miR-SNPs that were associated with EC risk. Despite the promising applicability of these miR-SNPs as disease biomarkers, they still lack validation in non-Asian populations. Moreover, there should be more pathway-based approaches to evaluate the cumulative effect of multiple unfavorable genotypes and, consequently, identify miR-SNPs signatures capable of predicting EC therapy response and prognosis. Full article
(This article belongs to the Special Issue MicroRNA-Associated Cancer Metastasis)
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