Downregulation of RUVBL1 inhibits proliferation of lung adenocarcinoma cells by G1/S phase cell cycle arrest via multiple mechanisms
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Lung cancer remains a leading cause of cancer-related mortality and morbidity worldwide, of which non-small cell lung cancer (NSCLC) accounts for 80 %. RUVBL1 is a highly conserved eukaryotic AAA+ adenosine 5′-triphosphatase (ATPase) that has many functions highly relevant to cancer. We therefore attempted to determine the potential role of RUVBL1 in the biogenesis of lung adenocarcinoma and obtained some interesting results. Our study revealed that RUVBL1 expression was higher in lung adenocarcinoma specimens than in those of adjacent non-tumor tissues and in lung cancer cell lines than in normal lung cell lines. RUVBL1 knockdown via siRNA reduced proliferation and caused G1/S phase cell cycle arrest in lung adenocarcinoma cell lines. The G1/S phase cell cycle arrest triggered by RUVBL1 downregulation could be attributed, at least in part, to repression of the AKT/GSK-3β/cyclin D1 pathway and probably to the activation of IRE1α-mediated endoplasmic reticulum (ER) stress. We thus demonstrated for the first time that a knockdown of RUVBL1 could effectively inhibit the proliferation of lung adenocarcinoma A549 and H292 cells through the induction of G1/S phase cell cycle arrest via multiple mechanisms. These observations strongly suggested that RUVBL1 should be considered a promising target for the prevention or therapy of lung adenocarcinoma.
KeywordsRUVBL1 Lung adenocarcinoma G1/S cell cycle arrest A549 cells H292 cells AKT
This study was supported by the National Natural Science Foundation of China, with the grant identification number 31170720.
Compliance with ethical standards
All specimens were collected after the patients had given their informed consent to participate, and all of the experiments were approved by the institution’s Internal Review and Ethics boards. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Conflicts of interest
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