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Published on: October 27, 2020
Regulatory interplay of miR-361-5p/TWIST1/SOX4 axis modulating epithelial-mesenchymal transition cascades in
Shankun Zhao1, Maolei Shen1, Xin Li1
1Department of Urology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China.
Background:
Prostate cancer (PCa) progression and metastasis remain significant challenges in clinical oncology. miR-361-5p has been identified to function as an important tumor suppressor in multiple human malignancies. However, the clinical significance and biological role of miR-361-5p in PCa remain unclear.
Methods:
The present study was conducted to investigate the molecular mechanisms in metastatic PCa by using various experimental methods in vitro and in vivo.
Results:
miR-361-5p was significantly downregulated in PCa cells and tissues. Overexpression of miR-361-5p inhibited proliferation, migration, and invasion in vitro, and suppressed tumor growth and lung metastasis in vivo. Mechanistically, miR-361-5p directly targeted TWIST1, reducing its protein levels and transcriptional activity; restoration of TWIST1 rescued the metastatic phenotype, confirming functional targeting. Importantly, miR-361-5p also regulated SOX4 via TWIST1 and formed a negative feedback loop with SOX4, reinforcing the suppression of metastasis. This TWIST1/SOX4 axis drove a reversal of epithelial-mesenchymal transition, marked by increased E-cadherin and decreased Vimentin and Fibronectin expression.
Conclusions:
The present study, for the first time, suggests that miR-361-5p functions as a tumor suppressor in PCa by modulating the TWIST1/SOX4 axis and EMT. These insights offer new therapeutic avenues for targeting miRNAs in metastatic PCa.
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