Long Non-Coding RNA GATA6-AS1 Inhibits Proliferation and Promotes Apoptosis of Lung Adenocarcinoma Through Sponging miR-331-3p and Regulating SOCS1/JAK2/STAT3 Pathway

Abstract Background: Accumulating evidence has indicated the remarkable roles of long non-coding RNAs (lncRNAs) as oncogenes or tumor suppressors in many malignancies. The involvement of lncRNA GATA6-AS1 in cancers remains largely undiscovered. Herein, our research was aimed at elucidating the function and mechanism of GATA6-AS1 in lung adenocarcinoma (LUAD). Methods: Gene expression was measured through qRT-PCR and WB. Cell proliferation ratio was determined using CCK-8 and EdU assays. Cell apoptosis ratio was determined using TUNEL and flow cytometry assays. Molecular interactions were examined through RIP, RNA pull-down and luciferase reporter assays. Results: GATA6-AS1 expression was markedly down-regulated in LUAD cell lines. GATA6-AS1 could inhibit LUAD cell proliferation and promote cell apoptosis. Mechanistically, GATA6-AS1 was identified as the molecular sponge for miR-331-3p, whose knockdown in LUAD cells could reinforce the tumor-suppressing effects of GATA6-AS1 overexpression. Moreover, GATA6-AS1 functions as a competing endogenous RNA (ceRNA) through sequestering miR-331-3p to deregulate SOCS1, thus inhibiting JAK2/STAT3 signaling pathway and suppressing LUAD cell viability. Conclusions: These results demonstrate the tumor-suppressing function and mechanism of lncRNA GATA6-AS1 in LUAD cells. The axis of GATA6-AS1/miR-331-3p/SOCS1/JAK2/STAT3 can be adopted as a novel approach for LUAD treatment.