Long Non-coding RNA SOX2-OT Enhances Cancer Biological Traits Via Sponging to Tumor Suppressor MiR-122-3p and MiR-194-5p in Non-small Cell Lung Carcinoma

Overview

Journal Sci Rep

Specialty Science

Date 2023 Jul 31

PMID 37524903

Authors

Fatemeh Dodangeh

Zahra Sadeghi

Parichehr Maleki

Jamshid Raheb

Affiliations

Soon will be listed here.

Abstract

The oncogenic role of long non-coding RNA SOX2 overlapping transcript (SOX2-OT) has been demonstrated as a miRNA decay system that sponges tumor suppressor miRNA, including miR-122-3p in glioblastoma and miR-194-5p in glioblastoma, gastric, and colorectal cancers. However, the molecular function of SOX2-OT remains unknown in most cancers, including lung cancer. In the current study, we aimed to evaluate the downstream regulatory function of SOX2-OT in A549 and Calu-3 lung cancer cell lines. We knocked down SOX2-OT expression using an RNA interference system, which significantly decreased expression in A549 and Calu-3 cells. The expression of down-regulating miRNAs (miR-122-3p and miR-194-5p) was evaluated, revealing increased expression of miR-122-3p and miR-194-5p. Additionally, the expression of miRNAs downstream mRNA, including FOXO1 (Forkhead Box O1) and FOXA1 (Forkhead Box O1), changed. Recently, critical roles of FOXO1 and FOXA1 proteins in pathways involved in proliferation, metastasis and apoptosis have been demonstrated. Downstream changes in cellular traits were assessed using MTT, flow cytometry, metastasis and apoptosis assays. These assessments confirmed that the biological behaviors of lung cancer cells were influenced after SOX2-OT knockdown. In summary, the present study highlights the oncogenic role of SOX2-OT through the regulation of miR-122-3p/FOXO1 and miR-194-5p/FOXA1 pathways.

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References

Prensner J, Chinnaiyan A . The emergence of lncRNAs in cancer biology. Cancer Discov. 2011; 1(5):391-407. PMC: 3215093. DOI: 10.1158/2159-8290.CD-11-0209. View

Wang H, Meyer C, Fei T, Wang G, Zhang F, Liu X . A systematic approach identifies FOXA1 as a key factor in the loss of epithelial traits during the epithelial-to-mesenchymal transition in lung cancer. BMC Genomics. 2013; 14:680. PMC: 3852829. DOI: 10.1186/1471-2164-14-680. View

Teng Y, Kang H, Chu Y . Identification of an Exosomal Long Noncoding RNA SOX2-OT in Plasma as a Promising Biomarker for Lung Squamous Cell Carcinoma. Genet Test Mol Biomarkers. 2019; 23(4):235-240. DOI: 10.1089/gtmb.2018.0103. View

Su R, Cao S, Ma J, Liu Y, Liu X, Zheng J . Knockdown of SOX2OT inhibits the malignant biological behaviors of glioblastoma stem cells via up-regulating the expression of miR-194-5p and miR-122. Mol Cancer. 2017; 16(1):171. PMC: 5683208. DOI: 10.1186/s12943-017-0737-1. View

Xie W, Yuan S, Sun Z, Li Y . Long noncoding and circular RNAs in lung cancer: advances and perspectives. Epigenomics. 2016; 8(9):1275-87. DOI: 10.2217/epi-2016-0036. View

Siegel R, Miller K, Fuchs H, Jemal A . Cancer statistics, 2022. CA Cancer J Clin. 2022; 72(1):7-33. DOI: 10.3322/caac.21708. View

Theodorakis P, Lomonosova E, Chinnadurai G . Critical requirement of BAX for manifestation of apoptosis induced by multiple stimuli in human epithelial cancer cells. Cancer Res. 2002; 62(12):3373-6. View

Jazi M, Mansour Samaei N, Ghanei M, Shadmehr M, Mowla S . Overexpression of the non-coding SOX2OT variants 4 and 7 in lung tumors suggests an oncogenic role in lung cancer. Tumour Biol. 2016; 37(8):10329-38. DOI: 10.1007/s13277-016-4901-9. View

Paraskevopoulou M, Hatzigeorgiou A . Analyzing MiRNA-LncRNA Interactions. Methods Mol Biol. 2016; 1402:271-286. DOI: 10.1007/978-1-4939-3378-5_21. View

10.

Huarte M . The emerging role of lncRNAs in cancer. Nat Med. 2015; 21(11):1253-61. DOI: 10.1038/nm.3981. View

11.

Yoon H, Kim N . Diagnosis and management of high risk group for gastric cancer. Gut Liver. 2014; 9(1):5-17. PMC: 4282848. DOI: 10.5009/gnl14118. View

12.

Wolter K, Hsu Y, Smith C, Nechushtan A, Xi X, Youle R . Movement of Bax from the cytosol to mitochondria during apoptosis. J Cell Biol. 1998; 139(5):1281-92. PMC: 2140220. DOI: 10.1083/jcb.139.5.1281. View

13.

Liu S, Xu B, Yan D . Enhanced expression of long non-coding RNA Sox2ot promoted cell proliferation and motility in colorectal cancer. Minerva Med. 2016; 107(5):279-86. View

14.

Warren C, Wong-Brown M, Bowden N . BCL-2 family isoforms in apoptosis and cancer. Cell Death Dis. 2019; 10(3):177. PMC: 6384907. DOI: 10.1038/s41419-019-1407-6. View

15.

Qu F, Cao P . Long noncoding RNA SOX2OT contributes to gastric cancer progression by sponging miR-194-5p from AKT2. Exp Cell Res. 2018; 369(2):187-196. DOI: 10.1016/j.yexcr.2018.05.017. View

16.

Wei R, Ding C, Alarcon Rodriguez R, Mullor M . The SOX2OT/miR-194-5p axis regulates cell proliferation and mobility of gastric cancer through suppressing epithelial-mesenchymal transition. Oncol Lett. 2018; 16(5):6361-6368. PMC: 6202518. DOI: 10.3892/ol.2018.9433. View

17.

Zhu X, Li D, Yu F, Jia C, Xie J, Ma Y . miR-194 inhibits the proliferation, invasion, migration, and enhances the chemosensitivity of non-small cell lung cancer cells by targeting forkhead box A1 protein. Oncotarget. 2016; 7(11):13139-52. PMC: 4914347. DOI: 10.18632/oncotarget.7545. View

18.

Hou Z, Zhao W, Zhou J, Shen L, Zhan P, Xu C . A long noncoding RNA Sox2ot regulates lung cancer cell proliferation and is a prognostic indicator of poor survival. Int J Biochem Cell Biol. 2014; 53:380-8. DOI: 10.1016/j.biocel.2014.06.004. View

19.

Han L, Zhang W, Zhang B, Zhan L . Long non-coding RNA SOX2OT promotes cell proliferation and motility in human ovarian cancer. Exp Ther Med. 2018; 15(2):2182-2188. PMC: 5776615. DOI: 10.3892/etm.2017.5618. View

20.

Jazi M, Mansour Samaei N, Ghanei M, Shadmehr M, Mowla S . Identification of new SOX2OT transcript variants highly expressed in human cancer cell lines and down regulated in stem cell differentiation. Mol Biol Rep. 2015; 43(2):65-72. DOI: 10.1007/s11033-015-3939-x. View