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MicroRNAs and Long Noncoding RNAs in Tumor Microenvironment
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MicroRNAs and Long Noncoding RNAs in Tumor Microenvironment

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 21490

Special Issue Editor

Dr. Young-Ho Ahn

E-Mail Website
Guest Editor
Department of Molecular Medicine and Inflammation-Cancer Microenvironment Research Center, College of Medicine, Ewha Womans University, Seoul 07804, Republic of Korea
Interests: microRNAs and long noncoding RNAs in cancer; tumor microenvironment; lung cancer; metastasis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The tumor microenvironment is a complex cellular and non-cellular network system that influences tumorigenesis, progression, metastasis, and drug resistance. Cellular components of the tumor microenvironment include tumor cells, cancer-associated fibroblasts, vascular endothelial cells, infiltrated immune cells, etc. Along with the extracellular matrix, cytokines/chemokines, and hypoxic signals, these cellular components interact directly or indirectly to facilitate tumor initiation and progression. A huge body of research shows support for the crucial role played by microRNAs and long-noncoding RNAs in the interaction between tumor cells and the tumor microenvironment, including stromal cells such as cancer-associated fibroblasts and tumor-associated macrophages. Thus, elucidation of the roles of microRNAs and long noncoding RNAs in the tumor microenvironment would establish the foundation for microRNA- or long noncoding RNA-based tumor diagnostic and therapeutic strategies.

This Special Issue of IJMS will cover a selection of recent research topics and current review articles related to the role of microRNAs and long noncoding RNAs in tumor microenvironment. Up-to-date review articles, commentaries and experimental papers are all welcome.

Dr. Young-Ho Ahn
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • tumor microenvironment
  • microRNAs
  • long noncoding RNAs
  • tumor progression
  • metastasis
  • cancer-associated fibroblast
  • tumor-associated macrophages
  • extracellular matrix

Published Papers (6 papers)

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Research

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18 pages, 3039 KiB  
Article
Profiling and Functional Analysis of microRNA Deregulation in Cancer-Associated Fibroblasts in Oral Squamous Cell Carcinoma Depicts an Anti-Invasive Role of microRNA-204 via Regulation of Their Motility
by Saroj Rajthala, Anjie Min, Himalaya Parajuli, Kala Chand Debnath, Borghild Ljøkjel, Kristin Marie Hoven, Arild Kvalheim, Stein Lybak, Evelyn Neppelberg, Olav Karsten Vintermyr, Anne Christine Johannessen, Dipak Sapkota and Daniela Elena Costea
Int. J. Mol. Sci. 2021, 22(21), 11960; https://doi.org/10.3390/ijms222111960 - 04 Nov 2021
Cited by 4 | Viewed by 2132
Abstract
Background: Knowledge on the role of miR changes in tumor stroma for cancer progression is limited. This study aimed to investigate the role of miR dysregulation in cancer-associated fibroblasts (CAFs) in oral squamous cell carcinoma (OSCC). Methodology: CAF and normal oral fibroblasts (NOFs) [...] Read more.
Background: Knowledge on the role of miR changes in tumor stroma for cancer progression is limited. This study aimed to investigate the role of miR dysregulation in cancer-associated fibroblasts (CAFs) in oral squamous cell carcinoma (OSCC). Methodology: CAF and normal oral fibroblasts (NOFs) were isolated from biopsies of OSCC patients and healthy individuals after informed consent and grown in 3D collagen gels. Total RNA was extracted. Global miR expression was profiled using Illumina version 2 panels. The functional impact of altered miR-204 expression in fibroblasts on their phenotype and molecular profile was investigated using mimics and inhibitors of miR-204. Further, the impact of miR-204 expression in fibroblasts on invasion of adjacent OSCC cells was assessed in 3D-organotypic co-cultures. Results: Unsupervised hierarchical clustering for global miR expression resulted in separate clusters for CAF and NOF. SAM analysis identified differential expression of twelve miRs between CAF and NOF. Modulation of miR-204 expression did not affect fibroblast cell proliferation, but resulted in changes in the motility phenotype, expression of various motility-related molecules, and invasion of the adjacent OSCC cells. 3′ UTR miR target reporter assay showed ITGA11 to be a direct target of miR-204. Conclusions: This study identifies differentially expressed miRs in stromal fibroblasts of OSCC lesions compared with normal oral mucosa and it reveals that one of the significantly downregulated miRs in CAF, miR-204, has a tumor-suppressive function through inhibition of fibroblast migration by modulating the expression of several different molecules in addition to directly targeting ITGA11. Full article
(This article belongs to the Special Issue MicroRNAs and Long Noncoding RNAs in Tumor Microenvironment)
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Review

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19 pages, 1005 KiB  
Review
The Role of Long Non-Coding RNA and microRNA Networks in Hepatocellular Carcinoma and Its Tumor Microenvironment
by Tingting Shi, Asahiro Morishita, Hideki Kobara and Tsutomu Masaki
Int. J. Mol. Sci. 2021, 22(19), 10630; https://doi.org/10.3390/ijms221910630 - 30 Sep 2021
Cited by 21 | Viewed by 2909
Abstract
Hepatocellular carcinoma (HCC) is a common liver malignancy with high morbidity and poor prognosis. Long non-coding RNAs (lncRNAs) are involved in crucial biological processes of tumorigenesis and progression, and play four major regulatory roles, namely signal, decoy, guide, and scaffold, to regulate gene [...] Read more.
Hepatocellular carcinoma (HCC) is a common liver malignancy with high morbidity and poor prognosis. Long non-coding RNAs (lncRNAs) are involved in crucial biological processes of tumorigenesis and progression, and play four major regulatory roles, namely signal, decoy, guide, and scaffold, to regulate gene expression. Through these processes, lncRNAs can target microRNAs (miRNAs) to form lncRNA and miRNA networks, which regulate cancer cell proliferation, metastasis, drug resistance, and the tumor microenvironment. Here, we summarize the multifaceted functions of lncRNA and miRNA networks in the pathogenesis of HCC, the potential use of diagnostic or prognostic biomarkers, and novel therapeutic targets in HCC. This review also highlights the regulatory effects of lncRNA and miRNA networks in the tumor microenvironment of HCC. Full article
(This article belongs to the Special Issue MicroRNAs and Long Noncoding RNAs in Tumor Microenvironment)
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16 pages, 1436 KiB  
Review
MicroRNAs in Metastasis and the Tumour Microenvironment
by Carla Solé and Charles Henderson Lawrie
Int. J. Mol. Sci. 2021, 22(9), 4859; https://doi.org/10.3390/ijms22094859 - 04 May 2021
Cited by 12 | Viewed by 3027
Abstract
Metastasis is the process whereby cancer cells migrate from the primary tumour site to colonise the surrounding or distant tissue or organ. Metastasis is the primary cause of cancer-related mortality and approximately half of all cancer patients present at diagnosis with some form [...] Read more.
Metastasis is the process whereby cancer cells migrate from the primary tumour site to colonise the surrounding or distant tissue or organ. Metastasis is the primary cause of cancer-related mortality and approximately half of all cancer patients present at diagnosis with some form of metastasis. Consequently, there is a clear need to better understand metastasis in order to develop new tools to combat this process. MicroRNAs (miRNAs) regulate gene expression and play an important role in cancer development and progression including in the metastatic process. Particularly important are the roles that miRNAs play in the interaction between tumour cells and non-tumoral cells of the tumour microenvironment (TME), a process mediated largely by circulating miRNAs contained primarily in extracellular vesicles (EVs). In this review, we outline the accumulating evidence for the importance of miRNAs in the communication between tumour cells and the cells of the TME in the context of the pre-metastatic and metastatic niche. Full article
(This article belongs to the Special Issue MicroRNAs and Long Noncoding RNAs in Tumor Microenvironment)
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20 pages, 1407 KiB  
Review
Novel miRNA Targets and Therapies in the Triple-Negative Breast Cancer Microenvironment: An Emerging Hope for a Challenging Disease
by Amal Qattan
Int. J. Mol. Sci. 2020, 21(23), 8905; https://doi.org/10.3390/ijms21238905 - 24 Nov 2020
Cited by 35 | Viewed by 6219
Abstract
Treatment of triple-negative breast cancer (TNBC) remains challenging because of the heterogeneity of the disease and lack of single targetable driving mutations. TNBC does not rely on estrogen, progesterone or epidermal growth factor receptors and is associated with aggressive disease progression and poor [...] Read more.
Treatment of triple-negative breast cancer (TNBC) remains challenging because of the heterogeneity of the disease and lack of single targetable driving mutations. TNBC does not rely on estrogen, progesterone or epidermal growth factor receptors and is associated with aggressive disease progression and poor prognosis. TNBC is also characterized by resistance to chemotherapeutics, and response to immunotherapies is limited despite promising results in a subset of TNBC patients. MicroRNAs (miRNAs) have emerged as significant drivers of tumorigenesis and tumor progression in triple-negative breast cancer (TNBC) and present unique opportunities to target various components of the TNBC microenvironment for improved efficacy against this difficult to treat cancer. Effects of miRNAs on multiple targets may improve response rates in the context of this genetically and biologically heterogeneous disease. In this review, we offer a comprehensive view of miRNA regulation in TNBC, treatment challenges presented by TNBC in the context of the tumor microenvironment and stem cell subpopulations, and current and emerging miRNA-based therapeutic strategies targeting various components of the TNBC microenvironment. In addition, we offer insight into novel targets that have potential for treating TNBC through multiple mechanisms in the tumor microenvironment simultaneously and those that may be synergistic with standard chemotherapies. Full article
(This article belongs to the Special Issue MicroRNAs and Long Noncoding RNAs in Tumor Microenvironment)
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17 pages, 670 KiB  
Review
Diagnostic and Therapeutic Implications of microRNAs in Non-Small Cell Lung Cancer
by Young-Ho Ahn and Yoon Ho Ko
Int. J. Mol. Sci. 2020, 21(22), 8782; https://doi.org/10.3390/ijms21228782 - 20 Nov 2020
Cited by 25 | Viewed by 3319
Abstract
microRNAs (miRNAs), endogenous suppressors of target mRNAs, are deeply involved in every step of non-small cell lung cancer (NSCLC) development, from tumor initiation to progression and metastasis. They play roles in cell proliferation, apoptosis, angiogenesis, epithelial-to-mesenchymal transition, migration, invasion, and metastatic colonization, as [...] Read more.
microRNAs (miRNAs), endogenous suppressors of target mRNAs, are deeply involved in every step of non-small cell lung cancer (NSCLC) development, from tumor initiation to progression and metastasis. They play roles in cell proliferation, apoptosis, angiogenesis, epithelial-to-mesenchymal transition, migration, invasion, and metastatic colonization, as well as immunosuppression. Due to their versatility, numerous attempts have been made to use miRNAs for clinical applications. miRNAs can be used as cancer subtype classifiers, diagnostic markers, drug-response predictors, prognostic markers, and therapeutic targets in NSCLC. Many challenges remain ahead of their actual clinical application; however, when achieved, the use of miRNAs in the clinic is expected to enable great progress in the diagnosis and treatment of patients with NSCLC. Full article
(This article belongs to the Special Issue MicroRNAs and Long Noncoding RNAs in Tumor Microenvironment)
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16 pages, 884 KiB  
Review
Long Non-Coding RNAs as Regulators of Interactions between Cancer-Associated Fibroblasts and Cancer Cells in the Tumor Microenvironment
by Young-Ho Ahn and Jeong Seon Kim
Int. J. Mol. Sci. 2020, 21(20), 7484; https://doi.org/10.3390/ijms21207484 - 11 Oct 2020
Cited by 17 | Viewed by 2960
Abstract
Long non-coding RNAs (lncRNAs) regulate diverse physiological and pathological processes via post-transcriptional, post-translational, and epigenetic mechanisms. They are also involved in tumor initiation, progression, and metastasis by functioning as key players in the tumor microenvironment. Cancer-associated fibroblasts (CAFs) promote tumor initiation, progression, metastasis, [...] Read more.
Long non-coding RNAs (lncRNAs) regulate diverse physiological and pathological processes via post-transcriptional, post-translational, and epigenetic mechanisms. They are also involved in tumor initiation, progression, and metastasis by functioning as key players in the tumor microenvironment. Cancer-associated fibroblasts (CAFs) promote tumor initiation, progression, metastasis, drug resistance, and immunosuppression, which can be modulated by lncRNAs. LncRNAs regulate the intrinsic properties of CAFs or cancer cells intracellularly or function extracellularly through exosomal secretion. In-depth studies on the mechanisms of lncRNA functions will enable their clinical use as diagnosis/prognosis markers and therapeutic targets in cancer treatment. Full article
(This article belongs to the Special Issue MicroRNAs and Long Noncoding RNAs in Tumor Microenvironment)
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