A novel lncRNA-hidden polypeptide regulates malignant phenotypes and pemetrexed sensitivity in A549 pulmonary adenocarcinoma cells

IF 3 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Amino Acids Pub Date : 2024-02-13 DOI:10.1007/s00726-023-03361-7

Xiaobing Han, Liangxin Chen, Peng Sun, Xiuqing Wang, Qian Zhao, Lingfeng Liao, Dejin Lou, Nan Zhou, Yujun Wang

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Abstract

The advance of high-throughput sequencing enhances the discovery of short ORFs embedded in long non-coding RNAs (lncRNAs). Here, we uncovered the production and biological activity of lncRNA-hidden polypeptides in lung adenocarcinoma (LUAD). In the present study, bioinformatics was used to screen the lncRNA-hidden polypeptides in LUAD. Analysis of protein expression was done by western blot or immunofluorescence assay. The functions of the polypeptide were determined by detecting its effects on cell viability, proliferation, migration, invasion, and pemetrexed (PEM) sensitivity. The protein interactors of the polypeptide were analyzed by mass spectrometry after Co-immunoprecipitation (Co-IP) assay. The results showed that the lncRNA LINC00954 was confirmed to encode a novel polypeptide LINC00954-ORF. The polypeptide had tumor-suppressor features in A549 cells by repressing cell growth, motility and invasion. Moreover, the polypeptide enhanced PEM sensitivity and suppressed growth in A549/PEM cells. The protein interactors of this polypeptide had close correlations with RNA processing, amide metabolic process, translation, RNA binding, RNA transport, and DNA replication. As a conclusion, the LINC00954-ORF polypeptide embedded in lncRNA LINC00954 possesses tumor-suppressor features in A549 and PEM-resistant A549 cells and sensitizes PEM-resistant A549 cells to PEM, providing evidence that the LINC00954-ORF polypeptide is a potential anti-cancer agent in LUAD.

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一种新的lncRNA隐藏多肽调控A549肺腺癌细胞的恶性表型和培美曲塞的敏感性。

高通量测序技术的发展促进了嵌入长非编码 RNA（lncRNA）的短 ORF 的发现。在这里，我们发现了肺腺癌（LUAD）中隐藏的lncRNA多肽的产生和生物活性。本研究采用生物信息学方法筛选 LUAD 中的 lncRNA 隐藏多肽。蛋白质表达的分析是通过 Western 印迹或免疫荧光检测进行的。通过检测多肽对细胞活力、增殖、迁移、侵袭和培美曲塞（PEM）敏感性的影响，确定了多肽的功能。在共免疫沉淀（Co-IP）试验后，通过质谱分析了多肽的蛋白相互作用体。结果表明，lncRNA LINC00954被证实编码一种新型多肽LINC00954-ORF。该多肽在 A549 细胞中具有抑制细胞生长、运动和侵袭的肿瘤抑制功能。此外，该多肽还能增强 A549/PEM 细胞对 PEM 的敏感性并抑制其生长。该多肽的蛋白相互作用与 RNA 处理、酰胺代谢过程、翻译、RNA 结合、RNA 运输和 DNA 复制密切相关。综上所述，lncRNA LINC00954内含的LINC00954-ORF多肽在A549细胞和PEM耐药A549细胞中具有抑瘤特性，并能使PEM耐药A549细胞对PEM敏感，从而证明LINC00954-ORF多肽是一种潜在的LUAD抗癌药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Amino Acids 生物-生化与分子生物学

CiteScore

6.40

自引率

5.70%

发文量

审稿时长

2.2 months

期刊介绍： Amino Acids publishes contributions from all fields of amino acid and protein research: analysis, separation, synthesis, biosynthesis, cross linking amino acids, racemization/enantiomers, modification of amino acids as phosphorylation, methylation, acetylation, glycosylation and nonenzymatic glycosylation, new roles for amino acids in physiology and pathophysiology, biology, amino acid analogues and derivatives, polyamines, radiated amino acids, peptides, stable isotopes and isotopes of amino acids. Applications in medicine, food chemistry, nutrition, gastroenterology, nephrology, neurochemistry, pharmacology, excitatory amino acids are just some of the topics covered. Fields of interest include: Biochemistry, food chemistry, nutrition, neurology, psychiatry, pharmacology, nephrology, gastroenterology, microbiology