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Selenium-mediated gga-miR-29a-3p regulates LMH cell proliferation, invasion, and migration by targeting COL4A2
Xueyuan Hu1, Siran Tan1, Hang Yin1
1College of Veterinary Medicine, Northeast Agricultural University, Harbin, China. lishu@neau.edu.cn.
Abstract:
Selenium (Se) is an essential trace element that has several functions in cellular processes related to cancer prevention. While the cancericidal effect of Se has been reported in liver cancer, the mechanism has not been clarified. MiR-29a has widely been reported as a tumor suppressor; however, it also acts as a carcinogenic agent by increasing cell invasion in human epithelial cancer cells and hepatoma cells. In a previous study, we found that miR-29a-3p is a Se-sensitive miRNA. However, its effect in the chicken hepatocellular carcinoma cell line (LMH) is still unknown. In the present study, we found that the expression of miR-29a-3p in LMH cells was decreased by Se supplementation and increased under Se-deficient conditions. Flow cytometry and CCK-8 results suggested that Se decreased LMH cell proliferation induced by miR-29a-3p overexpression. Transwell and gap-closure assays implied that Se mediated LMH cell invasion and migration by downregulating miR-29a-3p. Quantitative real-time polymerase chain reaction and Western blotting results suggested that Se mitigated miR-29a-3p overexpression-induced LMH cell proliferation by downregulating CDK2, cyclin-D1, CDK6, and cyclin-E1. We further demonstrated that collagen type IV alpha 2 (COL4A2) is a target gene of miR-29a-3p. COL4A2 activates the RhoA/ROCK pathway to promote LMH cell invasion and migration. In conclusion, Se mediated miR-29a-3p overexpression induced LMH cell invasion and migration by targeting COL4A2 to inactivate the RhoA/ROCK pathway.
Insights
Selenium (Se) supplementation reduces hepatocellular carcinoma cell proliferation and invasion by downregulating miR-29a-3p. This mechanism involves targeting collagen type IV alpha 2 (COL4A2) and inactivating the RhoA/ROCK pathway, offering insights into Se
Area of Science:
- Molecular Biology
- Cancer Research
- Nutritional Biochemistry
Background:
- Selenium (Se) is an essential trace element involved in cancer prevention.
- MicroRNA-29a (miR-29a) exhibits context-dependent roles in cancer, acting as a tumor suppressor or promoter.
- The specific role of miR-29a-3p in chicken hepatocellular carcinoma (LMH cells) and its regulation by Se remain unclear.
Purpose of the Study:
- To investigate the effect of Se supplementation on miR-29a-3p expression in LMH cells.
- To elucidate the role of miR-29a-3p in Se-mediated regulation of LMH cell proliferation, invasion, and migration.
- To identify the molecular targets and pathways involved in Se's anti-cancer effects in LMH cells.
Main Methods:
- Quantitative real-time polymerase chain reaction (qRT-PCR) to measure miR-29a-3p expression.
- Cell proliferation assays (CCK-8) and flow cytometry.
- Cell invasion (Transwell) and migration (gap-closure) assays.
- Western blotting to assess protein expression (CDK2, cyclin-D1, CDK6, cyclin-E1, COL4A2, RhoA, ROCK).
- Bioinformatic analysis and luciferase reporter assays to confirm target gene interaction.
Main Results:
- Se supplementation decreased miR-29a-3p expression in LMH cells.
- Se mitigated miR-29a-3p overexpression-induced proliferation, invasion, and migration.
- Se downregulated cell cycle regulators (CDK2, cyclin-D1, CDK6, cyclin-E1) and collagen type IV alpha 2 (COL4A2).
- COL4A2 was identified as a direct target of miR-29a-3p, activating the RhoA/ROCK pathway.
Conclusions:
- Selenium exerts anti-cancer effects in chicken hepatocellular carcinoma by downregulating miR-29a-3p.
- The mechanism involves targeting COL4A2, leading to the inactivation of the RhoA/ROCK signaling pathway.
- This study clarifies Se's role in regulating miR-29a-3p and its downstream targets in liver cancer progression.
