NUCKS promotes cell proliferation and suppresses autophagy through the mTOR-Beclin1 pathway in gastric cancer
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(2020) 39:194
RESEARCH
Open Access
NUCKS promotes cell proliferation and suppresses autophagy through the mTORBeclin1 pathway in gastric cancer Erhu Zhao1,2,3,4†, Liying Feng1,4,5†, Longchang Bai1,2,6 and Hongjuan Cui1,2,3,4,5*
Abstract Background: Nuclear casein kinase and cyclin-dependent kinase substrate (NUCKS), a novel gene first reported in 2001, is a member of the high mobility group (HMG) family. Although very little is known regarding the biological roles of NUCKS, emerging clinical evidence suggests that the NUCKS protein can be used as a biomarker and therapeutic target in various human ailments, including several types of cancer. Methods: We first assessed the potential correlation between NUCKS expression and gastric cancer prognosis. Then functional experiments were conducted to evaluate the effects of NUCKS in cell proliferation, cell cycle, apoptosis and autophagy. Finally, the roles of NUCKS on gastric cancer were examined in vivo. Results: We found that NUCKS was overexpressed in gastric cancer patients with poor prognosis. Through manipulating NUCKS expression, it was observed to be positively associated with cell proliferation in vitro and in vivo. NUCKS knockdown could induce cell cycle arrest and apoptosis. Then further investigation indicated that NUCKS knockdown could also significantly induce a marked increase in autophagy though the mTOR-Beclin1 pathway, which could be was rescued by NUCKS restoration. Moreover, silencing Beclin1 in NUCKS knockdown cells or adding rapamycin in NUCKS-overexpressed cells also confirmed these results. Conclusions: Our findings revealed that NUCKS functions as an oncogene and an inhibitor of autophagy in gastric cancer. Thus, the downregulation or inhibition of NUCKS may be a potential therapeutic strategy for gastric cancer. Keywords: NUCKS, Autophagy, mTOR, Beclin1, Gastric cancer
Background Gastric cancer is the second most common cancer in China and the third leading cause of cancer-related deaths worldwide [1, 2]. Although surgery is still the most effective treatment modality for patients with resectable tumors, due to the low rates of early detection * Correspondence: [email protected] † Erhu Zhao and Liying Feng contributed equally to this work. 1 State Key Laboratory of Silkworm Genome Biology, College of Biotechnology, Southwest University, No.2 Tiansheng Road, Beibei District, Chongqing 400716, China 2 Cancer Center, Reproductive Medicine Center, Medical Research Institute, Southwest University, Chongqing 400716, China Full list of author information is available at the end of the article
and diagnosis, many patients with gastric cancer in China have very poor survival [3]. Therefore, there is a need to better elucidate the pathogenesis of gastric cancer by identifying useful biomarkers and novel targets for treatment. Nuclear casein kinase and cyclin-dependent kinase substrate (NUCKS), a novel gene first reported in 2001 [4], is a member of the high mobility group (HMG) family [5]. NUCKS is widespread in vertebrates [6], and plays a significant
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