MicroRNA miR-19b-3p mediated G protein γ subunit 7 (GNG7) loss contributes lung adenocarcinoma progression through activating Hedgehog signaling

Bioengineered

Xiang-cheng Zhang¹  Kui Zang¹  Zhi-hao Yu¹  Xia Zhao² 

[1] Department of Intensive Care Unit, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huaian, Jiangsu, PR Chin;Department of Ultrasound Medicine, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huaian, Jiangsu, PR Chin;

关键词: Human G protein gamma 7 (GNG7);    miR-19b-3p;    lung adenocarcinoma (LUAD);    Hedgehog signaling;   

DOI  :  10.1080/21655979.2021.1976896

来源: Taylor & Francis

【 摘 要 】

G protein γ subunit 7 (GNG7) is a subunit of heterotrimeric G protein. It has been demonstrated low expressed GNG7 in various cancers. Nevertheless, the role of GNG7 in lung adenocarcinoma (LUAD) remains unclear. In the present study, GNG7 expression in LUAD tissues and cell lines was analyzed by RT-qPCR, western blot and immunohistochemical. Kaplan–Meier analysis was performed for determining the prognostic value of GNG7 expression. Then, the function of GNG7 in LUAD progression was examined by cell proliferation, invasion and mouse xenograft assays. In addition, the underlying biological mechanisms of GNG7 in LUAD progression were explored via the bioinformatics analysis and experimental validation. We found GNG7 was markedly down-regulated in LUAD tissues and cell lines. Clinically, low expression of GNG7 was associated with the dismal prognosis of LUAD patients. Gain-of-function analysis showed that GNG7 overexpression inhibited proliferation and invasion of LUAD cell in vitro, and compromised tumor formation ability in vivo. Besides, mechanistic study revealed that overexpression of GNG7 affected the progression of LUAD via inhibiting activation of Hedgehog signaling. Moreover, bioinformatics prediction and experimental verification confirmed that GNG7 was targeted by miR-19b-3p, which was elevated expression in LUAD and promoting the progression of LUAD. Furthermore, rescue experiments demonstrated that GNG7 reintroduction weakened miR-19b-3p-mediated aggressive tumor phenotypes of LUAD cells. These findings suggested miR-19b-3p/GNG7 axis contributed to the progression of LUAD through Hedgehog signaling, which might be a potential therapeutic target for LUAD treatment.

【 授权许可】

CC BY