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微小 RNA miR-19b-3p 介导的 G 蛋白 γ 亚基 7(GNG7)缺失通过激活 Hedgehog 信号通路促进肺腺癌的进展。

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

机构信息

Department of Ultrasound Medicine, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian, Jiangsu, PR China.

Department of Intensive Care Unit, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian, Jiangsu, PR China.

出版信息

Bioengineered. 2021 Dec;12(1):7849-7858. doi: 10.1080/21655979.2021.1976896.

Abstract

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 , and compromised tumor formation ability . 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.

摘要

G 蛋白 γ 亚基 7(GNG7)是异三聚体 G 蛋白的一个亚基。已经证明,GNG7 在各种癌症中低表达。然而,GNG7 在肺腺癌(LUAD)中的作用仍不清楚。在本研究中,通过 RT-qPCR、western blot 和免疫组织化学分析 LUAD 组织和细胞系中的 GNG7 表达。通过 Kaplan-Meier 分析确定 GNG7 表达的预后价值。然后,通过细胞增殖、侵袭和小鼠异种移植实验检测 GNG7 在 LUAD 进展中的功能。此外,通过生物信息学分析和实验验证探索了 GNG7 在 LUAD 进展中的潜在生物学机制。我们发现 GNG7 在 LUAD 组织和细胞系中明显下调。临床上,GNG7 低表达与 LUAD 患者的预后不良有关。功能获得分析表明,GNG7 过表达抑制 LUAD 细胞的增殖和侵袭,并削弱肿瘤形成能力。此外,机制研究表明,GNG7 通过抑制 Hedgehog 信号通路的激活影响 LUAD 的进展。此外,生物信息学预测和实验验证证实 GNG7 是 miR-19b-3p 的靶标,miR-19b-3p 在 LUAD 中表达上调,促进 LUAD 的进展。此外,挽救实验表明,GNG7 的重新引入削弱了 miR-19b-3p 介导的 LUAD 细胞侵袭性肿瘤表型。这些发现表明,miR-19b-3p/GNG7 轴通过 Hedgehog 信号通路促进 LUAD 的进展,这可能是 LUAD 治疗的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b748/8806737/6a2041097e6f/KBIE_A_1976896_F0001_OC.jpg

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