Overexpression of the non-coding SOX2OT variants 4 and 7 in lung tumors suggests an oncogenic role in lung cancer

• Published in: Tumor biology Vol. 37; no. 8; pp. 10329 - 10338
• Main Authors: Saghaeian Jazi, Marie, Samaei, Nader Mansour, Ghanei, Mostafa, Shadmehr, Mohammad Behgam, Mowla, Seyed Javad
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.08.2016; Springer Nature B.V
• Subjects: Alternative Splicing; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cancer therapies; Carcinoma, Non-Small-Cell Lung - genetics; Female; Flow Cytometry; Genetic Variation; Humans; Lung cancer; Lung Neoplasms - genetics; Male; Middle Aged; Original Article; Polymerase Chain Reaction; Ribonucleic acid; RNA; RNA, Long Noncoding - genetics; Transcriptome; Up-Regulation; Upregulation; Carcinogenesis; Lung cancer; SOX2 overlapping transcript
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1007/s13277-016-4901-9

Despite the advances in cancer therapy, lung cancer still remains the most leading cause of cancer death worldwide. The long non-coding RNAs (lncRNAs) are recently introduced as novel regulators of human cancers. SOX2 overlapping transcript ( SOX2OT ) is a cancer-associated lncRNA gene that encodes different alternatively spliced transcripts. Here, we investigated the alterations in the preferential expression of different SOX2OT s in twenty non-small cell lung cancer (NSCLC) patients by real-time quantitative reverse transcription PCR (qRT-PCR) method. We observed preferential expression of SOX2OT4 and SOX2OT7 in lung tumor tissues. The quantitative gene expression analysis revealed that >30 % of NSCLC tumors express SOX2OT4 (mean = 7.6 times) and SOX2OT7 (mean = 5.9 times) more than normal tissues, with higher expression in squamous cell carcinoma. Further, we observed overexpression of pluripotency-associated transcription factor, SOX2 in 47 % of our samples concordant with SOX2OT ( R  = 0.62, P value <0.05). Overexpression of OCT4A gene was also observed in 36.8 % of tumor tissues. Then, we investigated the effects of SOX2OT suppression in lung adenocarcinoma cell line, by means of RNAi. Cell characteristics of colony formation, apoptosis, 2-D mobility, and cell cycle progression were measured in control and treated A549 cells. The SOX2OT knockdown significantly reduced the colony formation ability of cancer cells; however, no alterations in the rate of apoptosis were detected. On the other hand, SOX2OT -suppressed cells had elevated accumulation in G2/M phase of cell cycle and exhibited limited mobility. Altogether, our findings support a potential oncogenic role for SOX2OT in non-small cell lung cancer tumor genesis and SOX2OT seems a promising therapeutic candidate for NSCLC.