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MiR-141-3p promotes malignant progression in prostate cancer through AlkB homolog 5-mediated m6A modification of protein arginine methyltransferase 6

生物 癌症研究 蛋白质精氨酸甲基转移酶5 甲基转移酶 小RNA 前列腺癌 癌症 精氨酸 AlkB 分子生物学 甲基化 生物化学 基因 DNA修复 遗传学 氨基酸
作者
Xiaohu Ge,Xun Li,Bide Liu,Shuheng Wang,Jiuzhi Li
出处
期刊:Chinese Journal of Physiology [Medknow Publications]
卷期号:66 (1): 43-43 被引量:5
标识
DOI:10.4103/cjop.cjop-d-22-00071
摘要

Prostate cancer (PCa) is one of the leading causes of cancer-related death in males worldwide and exploring more reliable biomarkers for PCa is essential for the diagnosis and therapeutics for the disease. Although the functions of miR-141-3p and AlkB homolog 5 (ALKBH5) were identified in some cancers, whether they were involved in the development of PCa remains unclear. In this study, reverse transcription-quantitative polymerase chain reaction unveiled that the expression of ALKBH5 was reduced in PCa tissues and was negatively correlated with miR-141-3p. ALKBH5 attenuated the malignant development of PCa through suppressing the growth, migration, invasion, and sphere formation abilities of PCa cells. In addition, the luciferase activity assay identified that ALKBH5 was corroborated as a downstream target of miR-141-3p. Moreover, miR-141-3p expression was boosted in PCa tissues and cells and inhibition of miR-141-3p suppressed the tumor growth of PCa in vivo. Moreover, ALKBH5 was confirmed to suppress protein arginine methyltransferase 6 (PRMT6) expression through N6-methyladenosine (m6A) modification. We further identified that miR-141-3p-modulated PRMT6 level through mediating ALKBH5. Furthermore, PRMT6 level was positively correlated with miR-141-3p level and negatively associated with ALKBH5 level. Finally, rescue assays also uncovered that miR-141-3p aggravated PCa development by regulating PRMT6. In conclusion, miR-141-3p accelerated the malignant progression of PCa through ALKBH5-mediated m6A modification of PRMT6, which might offer a novel insight into the role of miR-141-3p and ALKBH5 in the treatments of PCa patients.
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