Downregulation of long non‑coding RNA GACAT1 suppresses proliferation and induces apoptosis of NSCLC cells by sponging microRNA‑422a

Abstract

Increasing evidence has demonstrated the important roles of long non-coding (lnc) RNA in non-small cell lung cancer (NSCLC). lncRNA gastric cancer-associated transcript 1 (GACAT1) has been reported to play an oncogenic role in different types of cancer; however, the function of GACAT1 in NSCLC remains unclear. The present study found that GACAT1 was overexpressed in NSCLC tissues and was associated with poor outcomes in patients with NSCLC. Functional experiments revealed that GACAT1 downregulation inhibited proliferation, induced apoptosis and cell cycle arrest of 2 NSCLC cell lines. GACAT1 was found to target microRNA(miR)-422a mechanically and negatively regulated miR-422a expression. Reduced expression of miR-422a in NSCLC tissues was inversely correlated with that of GACAT1. Furthermore, YY1 transcription factor (YY1) was identified as a downstream miR-422a target. Reduced expression of GACAT1 inactivated YY1 by sponging miR-422a in NSCLC cells. YY1 reintroduction reversed the reduced proliferation of NSCLC cells via GACAT1 knockdown. Taken together, these results revealed the novel role of the GACAT1/miR-422a pathway in the progression of NSCLC cell lines, providing a possible therapeutic strategy for NSCLC treatment.

LncRNA GACAT1 induces tongue squamous cell carcinoma migration and proliferation via miR‐149

“…LncRNA NKILA suppressed invasion and migration of TSCC cell through inhibiting epithelial‐mesenchymal transition 33 . Recently, Zhong et al 34 showed that GACAT1 was decreased in NSCLC tissues, and knockdown of GACAT1 inhibited cell growth and promoted apoptosis via suppressing miR‐422a. Wang et al 35 indicated that GACAT1 induced breast tumour progression via sponging miR‐875‐3p.…”

Long Noncoding RNA TFAP2A-AS1 Exerts Promotive Effects in Non-Small Cell Lung Cancer Progression Via Controlling the microRNA-548a-3p/CDK4 axis as a Competitive Endogenous RNA

“…Considerable evidences suggest that lncRNAs perform core functions in a broad spectrum of biological phenotype in NSCLC. For instance, lncRNAs CCAT1 [21], PART1 [22] and GACAT1 [23] are overexpressed in NSCLC, thus exerting pro-oncogenic actions. Instead, downregulated LINC00476 [24], MEG3 [25] and WT1-AS [26] in NSCLC are certified as anti-carcinogenic lncRNAs.…”

Epigenetic Alterations and Inflammation as Emerging Use for the Advancement of Treatment in Non-Small Cell Lung Cancer

“…LncRNA gastric cancer−associated transcript 1 (GACAT1) was upregulated in NSCLC tissues and associated with survival. Mechanically, GACAT1 can negatively regulate miR−422a with YY1 transcription factor as a downstream target ( 105 ). Moreover, Circular RNA hsa_circ_0008305 (circPTK2) and transcriptional intermediary factor 1 γ (TIF1γ) were verified considerably downregulated in NSCLC cells undergoing EMT and tumor metastasis induced by TGF-β, indicating circPTK2 as a prospective therapeutic target for advanced NSCLC ( 106 ).…”