LINC00346 Sponges miR-30c-2-3p to Promote the Development of Lung Adenocarcinoma by Targeting MYBL2 and Regulating CELL CYCLE Signaling Pathway

Abstract

BackgroundLINC00346 has recently been reported to regulate the development of several cancer types, but its biological functions and underlying mechanisms in lung adenocarcinoma (LUAD) have not been elucidated. The purpose of this study was to investigate the molecular mechanism of LINC00346 in the progression of LUAD.MethodsBioinformatics was performed to find the target lncRNA, miRNA and mRNA, and the binding relationship between the target genes was verified by dual luciferase reporter gene and RIP assays. Fluorescence in situ hybridization was used to detect the location of LINC00346 in LUAD tissues. The expressions of LINC00346, miR-30c-2-3p and MYBL2 in each group were detected by qRT-PCR, and western blot was performed to detect expressions of MYBL2 and CELL CYCLE related proteins. Proliferation, metastasis, apoptosis and cell cycle of LUAD cells were detected by CCK-8, colony formation, Transwell and flow cytometry assays, respectively. Mouse xenograft models were established to further determine the effects of LINC00346 on LUAD tumor growth in vivo.ResultsLINC00346 was upregulated in LUAD tissues and cells and was mainly localized in the cytoplasm. Knockdown of LINC00346 inhibited tumor growth in vivo, proliferation, metastasis and cell cycle progression, while induced apoptosis. LINC00346 sponged miR-30c-2-3 by targeting MYBL2 and regulating CELL CYCLE signaling pathway. Inhibiting miR-30c-2-3p or overexpressing MYBL2 could reverse the inhibitory effect of LINC00346 knockdown on LUAD process.ConclusionsLINC00346 as a ceRNA played a carcinogenic role in the development of LUAD via miR-30c-2-3p/MYBL2 axis regulating the CELL CYCLE signaling pathway. The study generally elucidated the mechanism by which LINC00346 regulated the development of LUAD, providing new ideas for the diagnosis and treatment of LUAD guided by lncRNA.

New Insights into LINC00346 and its Role in Disease

“…The upregulation of LINC00346 has been found to promote cell proliferation and inhibit cell apoptosis in many diseases. Silencing LINC00346 has been found to obviously inhibit cell proliferation and promote cell apoptosis in bladder cancer (Ye et al, 2017), lung cancer (Wang et al, 2017;Xu et al, 2021), (Jin et al, 2020;Yin et al, 2020) HCC, glioma , (Li T. et al, 2020) CRC, and breast cancer (Li et al, 2020d). Additionally, several studies have revealed that elevated LINC00346 expression enhances cell proliferation in gastric cancer (Xu et al, 2019) and pancreatic cancer (Zhang et al, 2018;Peng et al, 2019;Shi et al, 2019).…”

“…Additionally, several studies have revealed that elevated LINC00346 expression enhances cell proliferation in gastric cancer (Xu et al, 2019) and pancreatic cancer (Zhang et al, 2018;Peng et al, 2019;Shi et al, 2019). Cell cycle arrest induced by LINC00346 has been observed in bladder cancer (Ye et al, 2017), lung cancer (Wang et al, 2017;Xu et al, 2021), (Jin et al, 2020) HCC, gastric cancer (Xu et al, 2019), and pancreatic cancer (Shi et al, 2019). Knockdown of LINC00346 facilitates G1/G0 cell cycle arrest in bladder cancer (Ye et al, 2017), non-small-cell lung cancer (Wang et al, 2017;Xu et al, 2021), and (Jin et al, 2020)HCC.…”

“…Cell cycle arrest induced by LINC00346 has been observed in bladder cancer (Ye et al, 2017), lung cancer (Wang et al, 2017;Xu et al, 2021), (Jin et al, 2020) HCC, gastric cancer (Xu et al, 2019), and pancreatic cancer (Shi et al, 2019). Knockdown of LINC00346 facilitates G1/G0 cell cycle arrest in bladder cancer (Ye et al, 2017), non-small-cell lung cancer (Wang et al, 2017;Xu et al, 2021), and (Jin et al, 2020)HCC. In gastric cancer, increased LINC00346 levels suppress cell cycle arrest at the G1-S phase (Xu et al, 2019) transition.…”

“…In gastric cancer, increased LINC00346 levels suppress cell cycle arrest at the G1-S phase (Xu et al, 2019) transition. The cell cycle is blocked in the G2/M phase with upregulated LINC00346 expression in pancreatic cancer (Shi et al, 2019) and lung adenocarcinoma (Xu et al, 2021).…”

“…Cell motility is a highly regulated mechanical process important in wound healing, metastasis, and embryogenesis (Selmeczi et al, 2005;Yip et al, 2007;Mejean et al, 2009). Increased expression of LINC00346 has been found to promote tumor cell metastasis in bladder cancer (Ye et al, 2017), lung cancer (Xu et al, 2021), (Jin et al, 2020;Yin et al, 2020;Zhang and Chen, 2020) HCC, glioma , (Li T. et al, 2020;Zhao et al, 2020) CRC, cutaneous squamous cell carcinoma (Piipponen et al, 2020), gastric cancer (Xu et al, 2019), and pancreatic cancer (Peng et al, 2019). LINC00346 significantly enhances cell migration and invasion in lung adenocarcinoma (Xu et al, 2021), (Jin et al, 2020;Yin et al, 2020;Zhang and Chen, 2020) HCC, glioma , (Li T. et al, 2020;Zhao et al, 2020)CRC, gastric cancer (Xu et al, 2019), and pancreatic cancer (Peng et al, 2019).…”