LncRNA HIF1A-AS2 accelerates malignant phenotypes of renal carcinoma by modulating miR-30a-5p/SOX4 axis as a ceRNA.
LncRNA HIF1A-AS2 accelerates malignant phenotypes of renal carcinoma by modulating miR-30a-5p/SOX4 axis as a ceRNA.
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LncRNA HIF1A-AS2 通过调节 miR-30a-5p/SOX4 轴作为 ceRNA 加速肾癌的恶性表型
DOI：
10.20892/j.issn.2095-3941.2020.0209
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发表时间：
2021-03-12
影响因子：
5.5
通讯作者：
Hou J
中科院分区：
文献类型：
--
作者：
Chen M;Wei X;Shi X;Lu L;Zhang G;Huang Y;Hou J
目的：多项报道提出lncRNA作为潜在的生物标志物参与恶性肿瘤的进展和生长。 HIF1A-AS2是一种新型lncRNA和潜在的生物标志物，参与癌症的发生和发展。然而，HIF1A-AS2在肾癌中的分子机制尚不清楚。方法：采用RT-qPCR检测肾癌组织和细胞系中HIF1A-AS2和miR-30a-5p的相对表达水平。利用功能丧失和过度表达，表征了 HIF1A-AS2 和 miR-30a-5p 在肾癌进展中的生物学效应。采用双荧光素酶报告基因分析和Western blot检测HIF1A-AS2在肾癌中的潜在机制。结果：与癌旁组织相比，肾癌组织中HIF1A-AS2表达上调（P < 0.05）。此外，肿瘤大小、肿瘤淋巴结转移分期和分化程度与HIF1A-AS2表达密切相关（P < 0.05）。 HIF1A-AS2 的敲低或过表达可抑制或促进肾癌细胞的恶性表型和 WNT/β-catenin 信号传导（P < 0.05）。 MiR-30a-5p 在肾癌中下调，并部分逆转恶性肾肿瘤细胞中的 HIF1A-AS2 功能。 HIF1A-AS2 作为 microRNA 海绵，主动调节海绵 miR-30a-5p 中 SOX4 的相对表达，随后增加肾癌的恶性表型。 HIF1A-AS2 显示出致癌作用，而 miR-30a-5p 在肾癌的发病机制中充当抗癌基因作用的拮抗剂。结论：HIF1A-AS2-miR-30a-5p-SOX4轴与肾癌的恶性进展和发展相关。肾癌中 HIF1A-AS2 的相对表达量与 miR-30a-5p 的表达量呈负相关，且与 SOX4 mRNA 水平密切相关。
Objective: Several reports have proposed that lncRNAs, as potential biomarkers, participate in the progression and growth of malignant tumors. HIF1A-AS2 is a novel lncRNA and potential biomarker, involved in the genesis and development of carcinomas. However, the molecular mechanism of HIF1A-AS2 in renal carcinoma is unclear. Methods: The relative expression levels of HIF1A-AS2 and miR-30a-5p were detected using RT-qPCR in renal carcinoma tissues and cell lines. Using loss-of-function and overexpression, the biological effects of HIF1A-AS2 and miR-30a-5p in kidney carcinoma progression were characterized. Dual luciferase reporter gene analysis and Western blot were used to detect the potential mechanism of HIF1A-AS2 in renal carcinomas. Results: HIF1A-AS2 was upregulated in kidney carcinoma tissues when compared with para-carcinoma tissues (P < 0.05). In addition, tumor size, tumor node mestastasis stage and differentiation were identified as being closely associated with HIF1A-AS2 expression (P < 0.05). Knockdown or overexpression of HIF1A-AS2 either restrained or promoted the malignant phenotype and WNT/β-catenin signaling in renal carcinoma cells (P < 0.05). MiR-30a-5p was downregulated in renal cancers and partially reversed HIF1A-AS2 functions in malignant renal tumor cells. HIF1A-AS2 acted as a microRNA sponge that actively regulated the relative expression of SOX4 in sponging miR-30a-5p and subsequently increased the malignant phenotypes of renal carcinomas. HIF1A-AS2 showed a carcinogenic effect and miR-30a-5p acted as an antagonist of the anti-oncogene effects in the pathogenesis of renal carcinomas. Conclusions: The HIF1A-AS2-miR-30a-5p-SOX4 axis was associated with the malignant progression and development of renal carcinoma. The relative expression of HIF1A-AS2 was negatively correlated with the expression of miR-30a-5p, and was closely correlated with SOX4 mRNA levels in renal cancers.
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