Inhibin βA is an independent prognostic factor that promotes invasion via Hippo signaling in non‑small cell lung cancer

Zhang,Yijun; Yan,Shumei; Li,Yan; Zhang,Jiangbo; Luo,Yuan; Li,Pengcheng; Yang,Yuanzhong; Li,Yong; Huang,Yuhua; Wang,Enhua

doi:10.3892/mmr.2021.12429

Inhibin βA is an independent prognostic factor that promotes invasion via Hippo signaling in non‑small cell lung cancer

Authors:
- Yijun Zhang
- Shumei Yan
- Yan Li
- Jiangbo Zhang
- Yuan Luo
- Pengcheng Li
- Yuanzhong Yang
- Yong Li
- Yuhua Huang
- Enhua Wang
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Affiliations: Department of Pathology, The First Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning 110010, P.R. China, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China, Department of Radiotherapy, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, P.R. China
Published online on: September 9, 2021 https://doi.org/10.3892/mmr.2021.12429
Article Number: 789
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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