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The distinct role of strand-specific miR-514b-3p and miR-514b-5p in colorectal cancer metastasis
Lin-Lin Ren1,2, Ting-Ting Yan1, Chao-Qin Shen1
1State Key Laboratory for Oncogenes and Related Genes; Division of Gastroenterology and Hepatology; Key Laboratory of Gastroenterology and Hepatology, Ministry of Health; Renji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, 200001, Shanghai, China.
Abstract:
The abnormal expression of microRNAs (miRNAs) in colorectal cancer (CRC) progression has been widely investigated. It was reported that the same hairpin RNA structure could generate mature products from each strand, termed 5p and 3p, which binds different target mRNAs. Here, we explored the expression, functions, and mechanisms of miR-514b-3p and miR-514b-5p in CRC cells and tissues. We found that miR-514b-3p was significantly down-regulated in CRC samples, and the ratio of miR-514b-3p/miR-514b-5p increased from advanced CRC, early CRC to matched normal colorectal tissues. Follow-up functional experiments illustrated that miR-514b-3p and miR-514b-5p had distinct effects through interacting with different target genes: MiR-514b-3p reduced CRC cell migration, invasion and drug resistance through increasing epithelial marker and decreasing mesenchymal marker expressions, conversely, miR-514b-5p exerted its pro-metastatic properties in CRC by promoting EMT progression. MiR-514b-3p overexpressing CRC cells developed tumors more slowly in mice compared with control cells, however, miR-514b-5p accelerated tumor metastasis. Overall, our data indicated that though miR-514b-3p and miR-514b-5p were transcribed from the same RNA hairpin, each microRNA has distinct effect on CRC metastasis.
Insights
MicroRNAs miR-514b-3p and miR-514b-5p, derived from the same precursor, exhibit opposing roles in colorectal cancer (CRC) metastasis. miR-514b-3p suppresses metastasis, while miR-514b-5p promotes it.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- MicroRNAs (miRNAs) are crucial regulators in colorectal cancer (CRC) progression.
- Different mature miRNA products (5p and 3p) can arise from the same hairpin RNA precursor, targeting distinct messenger RNAs (mRNAs).
Purpose of the Study:
- To investigate the expression, functions, and mechanisms of miR-514b-3p and miR-514b-5p in colorectal cancer.
- To elucidate their distinct roles in CRC cell behavior and metastasis.
Main Methods:
- Analysis of miRNA expression in CRC tissues and cell lines.
- Functional experiments assessing cell migration, invasion, drug resistance, and epithelial-mesenchymal transition (EMT).
- In vivo tumor development studies in mice.
Main Results:
- miR-514b-3p was significantly downregulated in CRC tissues, with its ratio to miR-514b-5p increasing from advanced to normal tissues.
- miR-514b-3p inhibited CRC cell migration, invasion, and drug resistance by modulating epithelial and mesenchymal markers.
- miR-514b-5p promoted EMT and metastasis in CRC cells.
- Overexpression of miR-514b-3p slowed tumor growth in mice, whereas miR-514b-5p accelerated metastasis.
Conclusions:
- Despite originating from the same precursor, miR-514b-3p and miR-514b-5p exert opposing effects on colorectal cancer metastasis.
- miR-514b-3p acts as a tumor suppressor, while miR-514b-5p functions as a promoter of CRC metastasis.
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