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Downregulated miRNA-491-3p accelerates colorectal cancer growth by increasing uMtCK expression
Xingkui Tang1, Yukun Lin2, Jialin He1
1Department of General Surgery, Panyu District Central Hospital, Guangzhou, China.
Abstract:
Colorectal carcinoma (CRC) is the second most frequent cancer worldwide. MiR-491-3p, a tumor-suppressive microRNA (miRNA, miR), has been revealed to be abnormally expressed in CRC tissues. Meanwhile, up-regulated ubiquitous mitochondrial creatine kinase (uMtCK) contributes to CRC cell proliferation. Here we aim to explore whether aberrant miR-491-3p expression promotes CRC progression through regulating uMtCK. To this end, miR-491-3p and uMtCK levels were assessed in CRC tissues using quantitative real-time PCR (qRT-PCR). The biological roles of miR-491-3p and uMtCK in regulating CRC growth were evaluated using colony formation assay and mouse Xenograft tumour model. We found that miR-491-3p expression was decreased in CRC tissues compared with matched para-cancerous tissues, whereas uMtCK expression was increased. Functionally, miR-491-3p overexpression repressed SW480 cell growth, whereas miR-491-3p depletion accelerated SW620 cell proliferation and growth. Inversely, uMtCK positively regulated CRC cell proliferation. Mechanistically, miR-491-3p post-transcriptionally downregulated uMtCK expression by binding to 3'-UTR of uMtCK. Consequently, restoring uMtCK expression markedly eliminated the role of miR-491-3p in suppressing CRC growth. Collectively, miR-491-3p functions as a tumour suppressor gene by repressing uMtCK, and may be a potential target for CRC treatment.
Insights
MicroRNA-491-3p (miR-491-3p) acts as a tumor suppressor in colorectal cancer (CRC) by downregulating ubiquitous mitochondrial creatine kinase (uMtCK). Lower miR-491-3p and higher uMtCK levels promote CRC progression, suggesting therapeutic potential.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Colorectal carcinoma (CRC) is a major global health concern.
- Tumor-suppressive microRNA-491-3p (miR-491-3p) is dysregulated in CRC.
- Increased ubiquitous mitochondrial creatine kinase (uMtCK) expression promotes CRC cell proliferation.
Purpose of the Study:
- To investigate the role of aberrant miR-491-3p expression in colorectal cancer progression.
- To determine if miR-491-3p regulates uMtCK in CRC.
- To explore the potential of miR-491-3p as a therapeutic target for CRC.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) to assess miR-491-3p and uMtCK levels in CRC tissues.
- Colony formation assays and mouse xenograft models to evaluate the biological roles of miR-491-3p and uMtCK.
- Luciferase reporter assays to confirm the binding of miR-491-3p to the 3'-UTR of uMtCK.
Main Results:
- miR-491-3p expression was significantly decreased in CRC tissues, while uMtCK expression was increased.
- Overexpression of miR-491-3p inhibited CRC cell growth, whereas its depletion promoted proliferation.
- uMtCK positively regulated CRC cell proliferation, and miR-491-3p post-transcriptionally downregulated uMtCK.
- Restoring uMtCK expression abolished the tumor-suppressive effects of miR-491-3p.
Conclusions:
- miR-491-3p functions as a tumor suppressor in colorectal cancer by repressing uMtCK expression.
- The miR-491-3p/uMtCK axis represents a potential therapeutic strategy for CRC treatment.
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