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

• Published in: Amino acids Vol. 56; no. 1; p. 15
• Main Authors: Han, Xiaobing, Chen, Liangxin, Sun, Peng, Wang, Xiuqing, Zhao, Qian, Liao, Lingfeng, Lou, Dejin, Zhou, Nan, Wang, Yujun
• Format: Journal Article
• Language: English
• Published: Vienna Springer Vienna 13.02.2024; Springer Nature B.V; Springer
• Subjects: A549 Cells; Adenocarcinoma; Adenocarcinoma - drug therapy; Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Analytical Chemistry; Anticancer properties; antineoplastic agents; Antineoplastic drugs; bioactive properties; Biochemical Engineering; Biochemistry; Bioinformatics; Biological activity; Biomedical and Life Sciences; Cancer; Cell growth; Cell Line, Tumor; Cell migration; Cell Proliferation; Cell viability; DNA biosynthesis; DNA replication; fluorescent antibody technique; Gene Expression Regulation, Neoplastic; Humans; Immunofluorescence; Immunoprecipitation; Life Sciences; LINC00954-ORF; lncRNA-hidden polypeptides; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; lungs; Mass spectrometry; Mass spectroscopy; Neurobiology; Next-generation sequencing; Non-coding RNA; NSCLC; Open reading frames; Original; Original Article; PEM resistance; Pemetrexed - metabolism; Pemetrexed - pharmacology; Peptides - metabolism; Phenotype; Phenotypes; Polypeptides; precipitin tests; protein synthesis; Proteins; Proteomics; Ribonucleic acid; RNA; RNA processing; RNA transport; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Sensitivity enhancement; Short ORFs; Tumors; Western blotting; lncRNA-hidden polypeptides; Short ORFs; NSCLC; LINC00954-ORF; PEM resistance
• ISSN: 1438-2199; 0939-4451; 1438-2199
• DOI: 10.1007/s00726-023-03361-7

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.