Abstract：
BACKGROUND: In recent years, significant attention has been directed towards long non-coding RNA NUT family member 2A antisense RNA 1 (NUTM2A-AS1) for its oncogenic role in tumours. This study aimed to investigate the functional and molecular mechanisms underlying NUTM2A-AS1 in prostate cancer (PCa).
METHODS: NUTM2A-AS1, miR-376a-3p, and protein arginine methyltransferase 5 (PRMT5) levels were assessed in PCa samples and matched non-cancerous prostate samples. The DU145 cell line was conditioned to undergo transfection with relevant plasmids, and a cell counting kit-8 assay was performed to evaluate cell proliferation. A Transwell assay was conducted to analyse cell migration or invasion. Cell apoptosis was assessed using an annexin V-fluorescein isothiocyanate/propidium iodide apoptosis detection kit and flow cytometry. A tumour sphere formation assay was conducted to assess the ability of PCa cells to form tumour spheres.
RESULTS: We found elevated expression of NUTM2A-AS1 and PRMT5 and decreased expression of miR-376a-3p in PCa samples. Inhibition of NUTM2A-AS1 or overexpression of miR-376a-3p led to reduced cell proliferation and diminished cancer stem cell-like traits in vitro. NUTM2A-AS1 regulated miR-376a-3p through competitive absorption, thereby modulating PRMT5. Up-regulation of PRMT5 nullified the therapeutic effects of inhibiting NUTM2A-AS1 or overexpressing miR-376a-3p in DU145 cells.
CONCLUSIONS: NUTM2A-AS1 promotes cancer stem cell-like traits in PCa cells by targeting PRMT5 through miR-376a-3p. Therefore, these NUTM2A-AS1-based novel insights into tumour therapy hold promise for patients with PCa.
METHODS: NUTM2A-AS1, miR-376a-3p, and protein arginine methyltransferase 5 (PRMT5) levels were assessed in PCa samples and matched non-cancerous prostate samples. The DU145 cell line was conditioned to undergo transfection with relevant plasmids, and a cell counting kit-8 assay was performed to evaluate cell proliferation. A Transwell assay was conducted to analyse cell migration or invasion. Cell apoptosis was assessed using an annexin V-fluorescein isothiocyanate/propidium iodide apoptosis detection kit and flow cytometry. A tumour sphere formation assay was conducted to assess the ability of PCa cells to form tumour spheres.
RESULTS: We found elevated expression of NUTM2A-AS1 and PRMT5 and decreased expression of miR-376a-3p in PCa samples. Inhibition of NUTM2A-AS1 or overexpression of miR-376a-3p led to reduced cell proliferation and diminished cancer stem cell-like traits in vitro. NUTM2A-AS1 regulated miR-376a-3p through competitive absorption, thereby modulating PRMT5. Up-regulation of PRMT5 nullified the therapeutic effects of inhibiting NUTM2A-AS1 or overexpressing miR-376a-3p in DU145 cells.
CONCLUSIONS: NUTM2A-AS1 promotes cancer stem cell-like traits in PCa cells by targeting PRMT5 through miR-376a-3p. Therefore, these NUTM2A-AS1-based novel insights into tumour therapy hold promise for patients with PCa.
摘要：
背景：近年来，长非编码RNANUT家族成员2A反义RNA1（NUTM2A-AS1）在肿瘤中的致癌作用受到了广泛关注。本研究旨在探讨NUTM2A-AS1在前列腺癌（PCa）中的功能和分子机制。
方法：NUTM2A-AS1，miR-376a-3p，在PCa样本和匹配的非癌前列腺样本中评估蛋白质精氨酸甲基转移酶5（PRMT5）水平。对DU145细胞系进行条件化，以进行相关质粒的转染，并进行细胞计数试剂盒-8测定以评估细胞增殖。进行Transwell测定以分析细胞迁移或侵袭。使用膜联蛋白V-异硫氰酸荧光素/碘化丙啶凋亡检测试剂盒和流式细胞术评估细胞凋亡。进行肿瘤球形成测定以评估PCa细胞形成肿瘤球的能力。
结果：我们发现PCa样本中NUTM2A-AS1和PRMT5的表达升高，miR-376a-3p的表达降低。NUTM2A-AS1的抑制或miR-376a-3p的过表达导致体外细胞增殖减少和癌症干细胞样性状减少。NUTM2A-AS1通过竞争性吸收调节miR-376a-3p，从而调节PRMT5。PRMT5的上调使在DU145细胞中抑制NUTM2A-AS1或过表达miR-376a-3p的治疗效果无效。
结论：NUTM2A-AS1通过miR-376a-3p靶向PRMT5促进PCa细胞的肿瘤干细胞样性状。因此,这些基于NUTM2A-AS1的肿瘤治疗新见解为PCa患者带来了希望。
方法：NUTM2A-AS1，miR-376a-3p，在PCa样本和匹配的非癌前列腺样本中评估蛋白质精氨酸甲基转移酶5（PRMT5）水平。对DU145细胞系进行条件化，以进行相关质粒的转染，并进行细胞计数试剂盒-8测定以评估细胞增殖。进行Transwell测定以分析细胞迁移或侵袭。使用膜联蛋白V-异硫氰酸荧光素/碘化丙啶凋亡检测试剂盒和流式细胞术评估细胞凋亡。进行肿瘤球形成测定以评估PCa细胞形成肿瘤球的能力。
结果：我们发现PCa样本中NUTM2A-AS1和PRMT5的表达升高，miR-376a-3p的表达降低。NUTM2A-AS1的抑制或miR-376a-3p的过表达导致体外细胞增殖减少和癌症干细胞样性状减少。NUTM2A-AS1通过竞争性吸收调节miR-376a-3p，从而调节PRMT5。PRMT5的上调使在DU145细胞中抑制NUTM2A-AS1或过表达miR-376a-3p的治疗效果无效。
结论：NUTM2A-AS1通过miR-376a-3p靶向PRMT5促进PCa细胞的肿瘤干细胞样性状。因此,这些基于NUTM2A-AS1的肿瘤治疗新见解为PCa患者带来了希望。
