期刊
CELL DEATH DISCOVERY
卷 7, 期 1, 页码 -出版社
SPRINGERNATURE
DOI: 10.1038/s41420-020-00387-8
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资金
- National Natural Science Foundation Project of China [81560416, 81874088]
- Cuiying Graduate Supervisor Applicant Training Program of Lanzhou University Second Hospital [CYDSPY201901]
- Cuiying Scientific and Technological Innovation Program of Lanzhou University Second Hospital [CY2017-MS11]
The study reveals that miR-541-3p enhances the radiosensitivity of prostate cancer cells by inhibiting HSP27 expression and downregulating beta-catenin.
Heat shock protein 27 (HSP27), a regulator of cell survival, can enhance the resistance of cancer cells to radiotherapy. As microRNA-541-3p (miR-541-3p) was recently predicted to be a putative upstream modulator of HSP27, the present study was designed to investigate the function and mechanism underlying how miR-541-3p modulates the radiosensitivity of prostate cancer (PCa) cells by regulating HSP27. Through quantitative PCR, miR-541-3p was determined to be poorly expressed in PCa tissues relative to normal controls, whereas its expression was enhanced after radiotherapy. Consistently, miR-541-3p expression levels in PCa cells were elevated after radiation. Cell viability and proliferation and apoptosis under radiation were subsequently evaluated in response to loss-of-function of miR-541-3p. It was found that inhibition of miR-541-3p facilitated the viability and proliferation of PCa cells and promoted their apoptosis post radiation, hence reducing the radiosensitivity of LNCaP cells. Dual-luciferase reporter assay identified that miR-541-3p negatively regulated the HSP27 mRNA expression by targeting its 3 ' -UTR. Meanwhile, miR-541-3p overexpression inhibited the beta -catenin expression by targeting HSP27. Furthermore, HSP27 or beta -catenin overexpression was noted to significantly reverse the miR-541-3p-mediated changes in the biological functions of PCa cells post radiation, suggesting that HSP27-dependent activation of beta -catenin might be the mechanism responsible for the promotive effect of miR-541-3p on radiosensitivity. Collectively, this study suggests that miR-541-3p specifically inhibits the HSP27 expression and downregulates beta -catenin, thereby enhancing the radiosensitivity of PCa cells. Our findings highlight the underlying mechanism of the miR-541-3p/HSP27/Wnt/beta -catenin axis regarding radiotherapy for PCa.
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