miR-541-3p enhances the radiosensitivity of prostate cancer cells by inhibiting HSP27 expression and downregulating β-catenin

Abstract

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 β-catenin expression by targeting HSP27. Furthermore, HSP27 or β-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 β-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 β-catenin, thereby enhancing the radiosensitivity of PCa cells. Our findings highlight the underlying mechanism of the miR-541-3p/HSP27/Wnt/β-catenin axis regarding radiotherapy for PCa.

The Influence of miRNAs on Radiotherapy Treatment in Prostate Cancer – A Systematic Review

“…More recently, miRNA-541-3p was studied in 33 PCa tissues and normal adjacent tissues before and after RT treatments. Interestingly, He et al found that miRNA-541-3p enhances the radiosensitivity of PCa by inhibiting HSP27 expression and downregulating β-catenin ( 51 ).…”

“…MiR-541-3p has low expression in PCa tissues, however, when submitted to RT is overexpressed in PCa cells (LNCaP, DU-145, PC3, and PrEC). Thus, using the mimic approach, miRNA-541-3p interacted directly with HSP27 and increased the radiosensitivity by enhanced apoptosis ( 51 ).…”

Inhibition of Wnt/β-Catenin Signaling Sensitizes Esophageal Cancer Cells to Chemoradiotherapy

“…The potential relevance of Wnt/β-catenin signaling in mediating RT/CRT resistance has been demonstrated in other tumor entities, including CRC [ 23 , 24 , 48 , 49 ], prostate cancer [ 50 ], lung cancer [ 51 ], head and neck cancer [ 52 ], breast cancer and mammary gland cells [ 53 ], nasopharyngeal cancer [ 54 ], glioblastoma [ 55 ], and pancreatic cancer [ 56 ]. Although these reports underpin the relevance of Wnt/β-catenin signaling for radioresistance, the underlying mechanisms are still not fully understood.…”

Sex differences in microRNA expression in first and third trimester human placenta

“…There were three male specific differentially expressed miRNAs across gestation from the miR-376 precursor, miR-376a-3p, miR-376a-5p, and miR-376b-3p, all upregulated in third trimester. All of these miRNAs have been associated with cancer including reproductive cancers [76-79], which may be suggestive that these miRNAs are under sex hormone control, which is fetal sex specific early in gestation during fetal sex differentiation [80, 81]. The sex specific differences across gestation in C14MC and C19MC may account for differences in the identified canonical pathways.…”