title: Overexpression of the non-coding SOX2OT variants 4 and 7 in lung tumors suggests an oncogenic role in lung cancer.
abstract: 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 SOX2OTs 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.
authors: Department of Molecular Medicine, Faculty of Advanced Medical Technologies, Golestan University of Medical Sciences, Gorgan, Iran.
authors: Marie
authors: M
authors: Saghaeian Jazi
authors: Stem Cell Research Center, Golestan University of Medical Sciences, Gorgan, Iran. n_samaei@yahoo.com.|Department of Human Genetics, Faculty of Advanced Medical Technologies, Golestan University of Medical Sciences, Gorgan, Iran. n_samaei@yahoo.com.
authors: Nader Mansour
authors: NM
authors: Samaei
authors: Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
authors: Mostafa
authors: M
authors: Ghanei
authors: Tracheal Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors: Mohammad Behgam
authors: MB
authors: Shadmehr
authors: Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran. sjmowla@modares.ac.ir.
authors: Seyed Javad
authors: SJ
authors: Mowla
mesh_terms: D017398:Alternative Splicing; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D014644:Genetic Variation; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D062085:RNA, Long Noncoding / Q000235:genetics*; D059467:Transcriptome; D015854:Up-Regulation
chemical_list: D062085:RNA, Long Noncoding; C000610979:long non-coding RNA Sox2ot, human
keywords: Carcinogenesis; Lung cancer; SOX2 overlapping transcript; Upregulation