Exosomal miRNAs as a Promising Source of Biomarkers in Colorectal Cancer Progression
Abstract
:1. Introduction
2. Colorectal Cancer Incidence and Diagnosis
3. Tumor Microenvironment and Exosomes
4. MicroRNAs
4.1. Packaging and Sorting miRNAs into Exosomes
4.2. The Role of Exosomal miRNAs in CRC Progression and Drug Resistance
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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miRNA | Function |
---|---|
miR-671-5p [94] | Oncogenic miR that is overexpressed in the large intestine of CRC patients and colorectal cancer cell lines. Its expression is associated with metastasis, proliferation, migration, and invasion of CRC cells. |
miR-193b [95] | Tumor-suppressive miR that is downregulated in the serum of CRC patients. Its low levels are correlated with TNM stage and metastasis in CRC patients. |
miR-1224-5p [96] | Tumor-suppressive miR that is reduced in CRC tissues and cell lines mainly due to the hypoxic microenvironment. It prevents the epithelial–mesenchymal transition (EMT), invasion, and migration of CRC cells by directly interfering with the SP1-mediated NF-κB pathway. |
miR-125b-1 [97] | Tumor-suppressive miR that is downregulated in early CRC cell lines. Its low levels induce metastasis by increasing the expression of the XIAP gene. |
miR-125a-3p [98] | Tumor-suppressive miR suppressing fucosyltransferase (FUT)5 and FUT6 to regulate the PI3K/Akt signaling pathway, subsequently inhibiting the proliferation, migration, invasion, and angiogenesis of CRC cells. It also inhibits CRC development by directly targeting the angiogenesis-related gene VEGFA and the antiapoptotic gene Bcl-2. |
miR-483-5p [99] | Tumor-suppressive miR that inhibits CRC cell proliferation and metastasis, possibly through inhibiting tumor necrosis factor-receptor associated factor (TRAF), which plays critical roles in immune cell signaling). |
miR-188-5p [100] | Oncogenic miR that is overexpressed in CRC tissue and cell lines. Its higher expression is accompanied by tumor cell proliferation, invasion, and metastasis through inhibition of FOXL1/Wnt signaling. |
miR-765 [101] | Tumor-suppressive miR that inhibits proliferation, migration, and invasion of CRC cells by targeting patatin-like protein 2 (PLP2). |
miR-638 [102] | Tumor-suppressive miR that is downregulated in the serum and within exosomes of CRC patients and cell lines. It represses CRC cell viability and migration and modulates the cell cycle by inhibiting tetraspanin 1 (TSPAN1). A reduction in miR-638 is associated with poor overall survival. |
miR-1246 [79] | Oncogenic miR that is involved in tumor progression and metastasis. miR-1246 targets normal p53; however, miR-1246 was found to be overexpressed in mutant p53 tumor-derived exosomes. |
miR-654-5p [103] | The abundant expression of miR-654-5p is correlated with colon cancer development, metastasis, and a low survival rate of CRC patients. |
miR-17 [104] | Overexpression of miR-17 can increase cell proliferation and liver metastases in CRC. It is also associated with the progression of colorectal adenoma to adenocarcinoma in CRC patients. |
miR-198 [105] | Tumor-suppressive miR that hinders CRC cell viability, triggers death, and inhibits metastasis. |
miR-601 and miR-760 [54] | Their expression was reduced in the serum of CRC patients, and they could be used as predictors of advanced CRC. |
miR-493-5p [106] | Tumor-suppressive miR that inhibits CRC progression by targeting the PI3K–Akt–FoxO3a signaling pathway. |
miR-223-3p [107] | Oncogenic miR that is upregulated in CRC tissues and associated with the proliferation and metastasis of CRC cells. |
miR-320 [108] | Tumor-suppressive miR that is downregulated in CRC tissues and cell lines. Its upregulation is associated with the inhibition of CRC cell proliferation and metastasis. Its downstream targets are FOXQ1 and SOX4 genes. |
miR-486-5p [109] | Tumor-suppressive miR that is downregulated in CRC tissues. It is a negative regulator of pleiomorphic adenoma gene-like 2 (PLAGL2), a transcription factor for β-catenin and insulin-like growth factor 2 (IGF2) with roles in promoting proliferation, cell survival, and metastasis, as well as decreasing E-cadherin and increasing N-cadherin expression. |
miR-150 [110] | Tumor-suppressive miR that is downregulated in serum exosomes of CRC patients; however, this expression was increased in postoperative samples. The downregulated expression was associated with higher tumor progression, metastasis, and poor survival rate. |
miR-100 [97] | When the expression of this tumor-suppressive miR decreased, CRC growth and metastasis increased. The mechanism involves the induction of downstream targets mTOR, IGF1R, Fas, and XIAP. |
miR-92a-3p [98] | Exosomal miR-92a-3p facilitates tumor angiogenesis by inducing partial EMT in endothelial cells and through the downregulation of Dkk-3 and claudin-11. Exosomes derived from colon cancer cells and plasma derived from murine xenograft models were enriched with miR-92a-3p, and it has been found to stimulate tube formation in human umbilical vein endothelial cells upon transfer. |
miR-193a [88] | The expression of this tumor-suppressive miR is abundantly increased in the exosomes of metastatic CRC cell lines and plasma of CRC patients with liver metastasis. Its upregulated expression is associated with a cell cycle arrest in the G1 phase followed by the hindering of CRC cell proliferation through the inhibition of Caprin1, followed by CCND2 and c-MYC. The loss of major vault protein (MVP) caused the upregulation of miR-193a in cells rather than exosomes. |
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Bakhsh, T.; Alhazmi, S.; Alburae, N.A.; Farsi, A.; Alzahrani, F.; Choudhry, H.; Bahieldin, A. Exosomal miRNAs as a Promising Source of Biomarkers in Colorectal Cancer Progression. Int. J. Mol. Sci. 2022, 23, 4855. https://doi.org/10.3390/ijms23094855
Bakhsh T, Alhazmi S, Alburae NA, Farsi A, Alzahrani F, Choudhry H, Bahieldin A. Exosomal miRNAs as a Promising Source of Biomarkers in Colorectal Cancer Progression. International Journal of Molecular Sciences. 2022; 23(9):4855. https://doi.org/10.3390/ijms23094855
Chicago/Turabian StyleBakhsh, Tahani, Safiah Alhazmi, Najla Ali Alburae, Ali Farsi, Faisal Alzahrani, Hani Choudhry, and Ahmed Bahieldin. 2022. "Exosomal miRNAs as a Promising Source of Biomarkers in Colorectal Cancer Progression" International Journal of Molecular Sciences 23, no. 9: 4855. https://doi.org/10.3390/ijms23094855