Abstract
Circular RNAs (circRNAs) are a specialized circular structure, are deregulated in cancers and play essential roles in biological processes involved in tumor progression. However, the mechanism by which circRNAs affect lung tumorigenesis and progression remains largely unexplored. To investigate the role of circRNA in lung cancer, circRNA expression profile was screened by bioinformatics analysis. The levels of circTAB2, miR-3142, and GLIS family zinc finger 2 (GLIS2) were measured by quantitate real-time (qRT-PCR) or western blot. Cell proliferation, apoptosis, migration and invasion were detected by EdU, flow cytometry, and transwell assays, respectively. Bioinformatics, western blot, RIP, pull down, dual luciferase reporter and rescue experiments were used to verify the direct relationship between miR-3142 and circTAB2 or GLIS2. The xenograft assays were used to assess the role of circTAB2 in vivo.CircTAB2 exhibited low expression in cancer tissues. Gain and loss-of-function assays indicated that circTAB2 could inhibit cell proliferation, migration and invasion. Functional studies revealed that circTAB2 acted as a miRNA sponge, directly interacted with miR-3142 and consequently regulated GLIS2 /AKT. Taken together, circTAB2 serves as an inhibitory role in lung cancer through a novel circTAB2 /miR-3142 /GLIS2 /AKT pathway and could be exploited a novel marker in lung cancer.
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Funding
This work was supported by National Key Research and Development Program (2022YFC3600100, 2019YFA0903802) to YW, high-level talents of Youjiang Medical College for Nationalities (YY2021SK02) to LJ.
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Youliang Wang, Lihe Jiang and Yanli Lin designed and supervised the manuscript. Weiling Man, Yumeng Cui, Yanghua Li, Jie Jin, Yang Jin, Xiaojie Wu, Rongbin Zhong, Xiang Li and He Yao collected the data and conducted the statistical analyses. Weiling Man wrote the manuscript. Jie Li collected the clinical sample. All authors read and approved the manuscript.
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Studies using human tissues and plasma samples were approved by the Ethics Committee of Chinese PLA General Hospital were performed in accordance with the principles of Declaration of Helsinki. The animal study was approved by the Animal Ethic Review Committees of Beijing Institute of Biotechnology. All animal experiments were strictly implemented in compliance with the NIH Guide for the Care and Use of Laboratory Animals.
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Man, W., Cui, Y., Li, J. et al. circTAB2 inhibits lung cancer proliferation, migration and invasion by sponging miR-3142 to upregulate GLIS2. Apoptosis 28, 471–484 (2023). https://doi.org/10.1007/s10495-022-01805-1
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DOI: https://doi.org/10.1007/s10495-022-01805-1