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CDX2/mir-145-5p/SENP1 Pathways Affect LNCaP Cells Invasion and Migration
Jin-Hua He1, Ze-Ping Han1, Mao-Xian Zou1
1Department of Laboratory Medicine, Central Hospital of Panyu District, Guangzhou, China.
Frontiers in Oncology
|June 29, 2019
Summary
MicroRNA-145-5p (miR-145-5p) suppresses prostate cancer progression by inhibiting cell invasion and migration. Its expression is reduced by transcription factor CDX2, which impacts SENP1 translation.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are implicated in tumorigenesis, with dysregulation observed in various cancers, including prostate cancer.
- miR-145-5p, a downregulated miRNA in prostate cancer, exhibits tumor-suppressive properties, but its mechanism of action needs further investigation.
Purpose of the Study:
- To elucidate the mechanism by which miR-145-5p exerts its tumor-suppressive effects in prostate cancer.
- To investigate the regulatory relationship between miR-145-5p, CDX2, and SENP1 in prostate cancer cells.
Main Methods:
- Overexpression of miR-145-5p in LNCaP prostate cancer cells using lentiviral vectors.
- Assays for cell proliferation (WST-8), apoptosis (flow cytometry), colony formation, invasion, and migration (Transwell).
- Western blotting for protein expression, bioinformatics (TargetScan, ChIPBase), qRT-PCR, reporter gene assays, 5' RACE, and ChIP to analyze molecular interactions.
Main Results:
- Overexpression of miR-145-5p inhibited proliferation, invasion, and migration while promoting apoptosis in LNCaP cells.
- miR-145-5p overexpression decreased SENP1 and CDX2 protein levels; CDX2 was found to bind the miR-145-5p promoter, inhibiting its transcription.
- miR-145-5p directly targets SENP1's 3'-UTR, inhibiting its translation.
Conclusions:
- CDX2 inhibits miR-145-5p expression, consequently reducing miR-145-5p's inhibition on SENP1 translation.
- This regulatory axis (CDX2-miR-145-5p-SENP1) influences prostate cancer cell invasion and migration.
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