RETRACTED ARTICLE: Circ_002117 binds to microRNA-370 and promotes endoplasmic reticulum stress-induced apoptosis in gastric cancer

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.

Subcellular Localization of miRNAs and Implications in Cellular Homeostasis

“…For example, the overexpression of miR-328-3p, targeting ER metalloprotease 1 (ERMP1), prevented liver cancer cell proliferation and invasion in female nude mice by reducing phosphorylation [92]. RT-qPCR analyses of biopsy specimens and cell lines verified that miR-370 is upregulated in gastric cancer, and Circ_002117 inhibits miR-370 to stimulate ER stress-induced apoptosis [93]. Moreover, ER stress-induced exosomal miRNAs also contribute to the pathogenesis of cancer.…”

Interplay between endoplasmic reticulum stress and non-coding RNAs in cancer

“…Augmented circ_002117 expression induced ER stress by upregulating the UPR pathway components GRP78, IRE1, eIF2α, and CHOP, subsequently resulting in apoptosis in gastric cancer cells. The underlying mechanism involves circ_002117 forming a sponge with miR-370, upregulating the HERPUD1 level, and facilitating ER stress-induced apoptosis [ 148 ]. CircCDR1as is highly expressed in OSCCs.…”

The Antitumor Effect of TPD52L2 Silencing on Oxaliplatin-Resistant Gastric Carcinoma Is Related to Endoplasmic Reticulum Stress In Vitro

“…We identified that the induction in caspase-3 and PARP-1 activation via TPD52L2 silencing might be a reason for the apoptotic-induced antitumor effect in gastric carcinoma cells (OXA resistant). It has been indicated that stimulation of ER stress can increase the apoptotic process and reduce the proliferation of gastric carcinoma cells [29]. In the existing study, we found the elevated expression level of PERK, GRP78, CHOP, and IRE1α in TPD52L2 knockdown OXA-resistant gastric carcinoma cells, as compared with the control siRNAtransfected cells.…”

“…It has been indicated that stimulation of ER stress can increase the apoptotic process and reduce the proliferation of gastric carcinoma cells [ 29 ]. In the existing study, we found the elevated expression level of PERK, GRP78, CHOP, and IRE1 α in TPD52L2 knockdown OXA-resistant gastric carcinoma cells, as compared with the control siRNA-transfected cells.…”