Circ_002117 binds to microRNA-370 and promotes endoplasmic reticulum stress-induced apoptosis in gastric cancer
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Cancer Cell International Open Access
PRIMARY RESEARCH
Circ_002117 binds to microRNA-370 and promotes endoplasmic reticulum stressinduced apoptosis in gastric cancer Nan Zhou1, Hui Qiao2, Miaomiao Zeng3, Lei Yang3, Yongning Zhou4,5 and Quanlin Guan5,6*
Abstract Background: Mounting evidence implicates circular RNAs (circRNAs) in various biological processes during cancer progression. Gastric cancer is a main cause of cancer-related deaths worldwide. Herein, we aimed at investigating whether circ_002117 mediates gastric cancer progression through endoplasmic reticulum (ER) stress. Methods: Bioinformatics analysis detected differentially expressed circRNAs and their target miRNA candidates, and RT-qPCR was performed to detect expression of circ_002117, microRNA (miRNA)-370 and HERPUD1 in gastric cancer tissues and cells. Gastric cancer cells were transfected with plasmids and their proliferative ability and apoptosis were detected with gain- and loss-of-function assay. The ER of treated cells was observed under a transmission electron microscope. Dual-luciferase reporter gene assay and RIP were performed to detect the interaction between HEPRUD1, miR-370 and circ_002117-treated cells were injected into mice to establish xenograft tumor model. Results: Circ_002117 and HEPRUD1 were poorly expressed whereas miR-370 was highly expressed in clinical cancer tissues and cells. Circ_002117 was indicated to target and suppress miR-370 expression, while HERPUD1 was directly targeted by miR-370. Circ_002117 overexpression or miR-370 deficiency promoted ER stress-induced apoptosis and decreased proliferation of gastric cancer cells, which was reversed by silencing of HEPRUD1. Circ_002117 overexpression or miR-370 depletion significantly suppressed gastric cancer tumorigenesis in vivo. Conclusions: Taken altogether, circ_002117 facilitated ER stress-induced apoptosis in gastric cancer by upregulating HERPUD1 through miR-370 inhibition. Keywords: CircularRNA-002117, microRNA-370, HERPUD1, Gastric cancer, Endoplasmic reticulum stress Background Gastric cancer is the fifth most common cancer and the third most common cause of cancer-related death on a global scale [1]. Due to the nature of gastric cancer, diagnosis is often made late in the disease course, such that many patients miss the best time for treatment [2]. Due to the usually late diagnosis, lymphatic metastasis and *Correspondence: [email protected] 5 Key Laboratory for Gastrointestinal Disease of Gansu Province, The First Hospital of Lanzhou University, Lanzhou 730000, People’s Republic of China Full list of author information is available at the end of the article
distant metastasis are the leading causes of death of gastric cancer patients [3]. Recent observations indicate that endoplasmic reticulum (ER) stress determines cancer cell fate by modulating cellular signaling networks during gastric cancer progression [4]. Classically, ER participates in the regulation of protein synthesis and maturation, calcium homeostasis and protein folding [5]. Aberrant accum
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