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Inhibin βA is an independent prognostic factor that promotes invasion via Hippo signaling in non‑small cell lung cancer.
Molecular Medicine Reports ( IF 3.4 ) Pub Date : 2021-09-10 , DOI: 10.3892/mmr.2021.12429
Yijun Zhang 1 , Shumei Yan 2 , Yan Li 3 , Jiangbo Zhang 2 , Yuan Luo 1 , Pengcheng Li 1 , Yuanzhong Yang 2 , Yong Li 2 , Yuhua Huang 2 , Enhua Wang 1
Affiliation  

Inhibin βA (INHBA) serves a prognostic and tumor‑promoting role in numerous types of cancer. The present study aimed to determine the clinical significance of INHBA in non‑small cell lung cancer (NSCLC) and the mechanisms underlying its potential tumor‑promoting effect. INHBA expression was detected in clinical NSCLC samples using immunohistochemistry. In vivo loss‑ and gain‑of‑function studies were performed to determine the effects of INHBA on NSCLC invasion. In addition, protein and mRNA expression levels of INHBA, yes‑associated protein (YAP), large tumor suppressor 1/2 kinase (LATS1/2), connective tissue growth factor, cysteine rich angiogenic inducer 61 and Merlin were assessed using western blotting and reverse transcription‑quantitative PCR, respectively, to investigate the mechanism by which INHBA may affect the invasion of NSCLC. The present study revealed that INHBA was significantly upregulated in 238 clinical NSCLC samples compared with its expression levels in paired adjacent non‑cancerous tissues, and in metastatic nodules compared with in primary tumors. Notably, high INHBA expression was statistically associated with clinicopathological features, including poor differentiation and advanced tumor stage. INHBA positivity was statistically related to decreased 5‑year overall survival, for which INHBA was an independent prognostic factor. Furthermore, INHBA promoted NSCLC invasion in vitro. In NSCLC, INHBA expression was associated with the nuclear levels of YAP and INHBA overexpression enhanced the invasive abilities of NSCLC cells via inhibiting the Hippo pathway. Mechanistically, INHBA inhibited l LATS1/2 phosphorylation and induced YAP nuclear translocation by downregulating the protein expression levels of Merlin. In conclusion, INHBA may negatively regulate the Hippo pathway to act as a tumor promotor, and could represent a marker of prognosis in NSCLC.

中文翻译:

抑制素 βA 是一种独立的预后因素,可通过 Hippo 信号传导促进非小细胞肺癌的侵袭。

抑制素 βA (INHBA) 在多种癌症中发挥预后和促进肿瘤的作用。本研究旨在确定 INHBA 在非小细胞肺癌 (NSCLC) 中的临床意义及其潜在促肿瘤作用的机制。使用免疫组织化学在临床 NSCLC 样品中检测 INHBA 表达。体内进行功能丧失和获得的研究以确定 INHBA 对 NSCLC 侵袭的影响。此外,使用蛋白质印迹法评估 INHBA、yes 相关蛋白 (YAP)、大肿瘤抑制因子 1/2 激酶 (LATS1/2)、结缔组织生长因子、富含半胱氨酸的血管生成诱导物 61 和 Merlin 的蛋白质和 mRNA 表达水平,以及分别进行逆转录定量PCR,以研究INHBA可能影响NSCLC侵袭的机制。本研究显示,与其在成对的相邻非癌组织中的表达水平相比,INHBA 在 238 个临床 NSCLC 样本中显着上调,在转移性结节中的表达水平与在原发性肿瘤中相比显着上调。值得注意的是,高 INHBA 表达与临床病理学特征在统计学上相关,包括分化差和肿瘤晚期。INHBA 阳性与 5 年总生存率降低有统计学相关,而 INHBA 是一个独立的预后因素。此外,INHBA 促进 NSCLC 侵袭体外。在 NSCLC 中,INHBA 表达与 YAP 的核水平相关,INHBA 过表达通过抑制 Hippo 通路增强了 NSCLC 细胞的侵袭能力。机制上,INHBA 通过下调 Merlin 的蛋白表达水平抑制 l LATS1/2 磷酸化并诱导 YAP 核转位。总之,INHBA 可能负调节 Hippo 通路作为肿瘤促进剂,并可能代表 NSCLC 的预后标志物。
更新日期:2021-09-10
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