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N6-甲基腺苷 RBM15 调节因子在肺腺癌中的预后价值。

The prognostic value of N6-methyladenosine RBM15 regulators in lung adenocarcinoma.

机构信息

Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan,650118, China.

Department of Cardiothoracic Surgery, The Sixth Affiliated Hospital of Kunming Medical University, Yuxi,Yunnan,653100, China.

出版信息

Cell Mol Biol (Noisy-le-grand). 2022 May 22;68(1):130-139. doi: 10.14715/cmb/2022.68.1.17.

Abstract

N6-methyladenosine (m6A) is the most common internal modification in mammalian mRNAs while RNA-binding motif protein 15 (RBM15) is an important methyltransferase in m6A modification. Increasing evidences have shown that RBM15 has a close correlation with lung cancer. However, specific functions of RBM15 in lung adenocarcinoma (LUAD) are limited. RBM15 expression was analyzed in human LUAD tissues and matched healthy lung tissue. RBM15 was knocked down via siRNA in A549 and H1734 cells. The relationships between RBM15 with cellular functions characteristics and mRNA m6A levels were explored. We performed functional characterization in A549 and H1734 cells lines to elucidate the molecular role of RBM15. Results found that RBM15 was up-regulated in the LUAD tissue and cells, which was linked to poor survival of LUAD patients. RBM15 can be knocked down via siRNA in A549, which leads to the exploration of the associations between RBM15 with cell characteristics. In vivo, RBM15 knockdown could decrease the methylation level, reduce proliferation, accelerate apoptosis and inhibit tumor growth. Our research shows that RBM15 facilitates LUAC cell progression by m6A demethylation. However, it is necessary to conduct further researches on potential downstream molecular mechanisms and m6A modification of RBM15 activity in LUAC.

摘要

N6-甲基腺苷(m6A)是哺乳动物 mRNA 中最常见的内部修饰,而 RNA 结合基序蛋白 15(RBM15)是 m6A 修饰的重要甲基转移酶。越来越多的证据表明,RBM15 与肺癌密切相关。然而,RBM15 在肺腺癌(LUAD)中的具体功能有限。分析了人 LUAD 组织和匹配的健康肺组织中的 RBM15 表达。通过 siRNA 在 A549 和 H1734 细胞中敲低 RBM15。探索了 RBM15 与细胞功能特征和 mRNA m6A 水平之间的关系。在 A549 和 H1734 细胞系中进行功能表征,以阐明 RBM15 的分子作用。结果发现,RBM15 在 LUAD 组织和细胞中上调,与 LUAD 患者的不良生存相关。可以通过 siRNA 在 A549 中敲低 RBM15,从而探索 RBM15 与细胞特征之间的关联。在体内,RBM15 敲低可降低甲基化水平、抑制增殖、促进细胞凋亡并抑制肿瘤生长。我们的研究表明,RBM15 通过 m6A 去甲基化促进 LUAC 细胞进展。然而,有必要进一步研究 RBM15 在 LUAC 中的潜在下游分子机制和 m6A 修饰活性。

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