The miR-370/UQCRC2 axis facilitates tumorigenesis by regulating epithelial-mesenchymal transition in Gastric Cancer

Abstract

Ubiquinol-cytochrome c reductase core protein 2 (UQCRC2) is an important mitochondrial complex III subunit. This study investigated the role of UQCRC2 in gastric cancer (GC) and its upstream regulatory microRNAs (miRNAs). UQCRC2 expression levels were lower in GC tissues than non-carcinoma tissues. Furthermore, UQCRC2 levels were negatively correlated with lymph node metastasis, relapse, and tumor grade. Bioinformatics analysis predicted UQCRC2 as the target gene for miR-370, and this was verified in luciferase reporter assays. MiR-370 levels were inversely correlated with UQCRC2 levels in GC. UQCRC2 overexpression suppressed GC cell migration and invasion in vitro and in vivo, whereas up-regulating miR-370 reversed these effects. Western blotting analysis showed that miR-370 targeted UQCRC2 and positively regulated the epithelial-mesenchymal transition (EMT) signaling pathway in GC cells. Therefore, the miR-370/UQCRC2 axis may regulate EMT signaling pathways to affect tumor proliferation and metastasis and is, thus, a potential target for GC treatment.

Circular RNA hsa_circ_0000751 serves as a microRNA-488 sponge to suppress gastric cancer progression via ubiquinol-cytochrome c reductase core protein 2 regulation

“…Our previous study revealed a weak presence of UQCRC2 in GC tissues, as evidenced by quantitative real-time polymerase chain reaction (qRT-PCR). We further confirmed the feasibility of using UQCRC2 as a stand-alone diagnostic biomarker for GC disease survival, wherein we found that the expression level of UQCRC2 showed a significant negative correlation with disease progression [ 14 ].…”

“…Using dual-luciferase reporter assays, we confirmed that miR-488 can directly target UQCRC2. In previous studies, we discovered that UQCRC2 expression remains substantially low in GC tissues and is correlated with a better prognosis in GC patients [ 14 ]. Here, we showed that UQCRC2 knockdown suppressed the hsa_circ_0000751-mediated action on the proliferation and invasion of GC cells.…”

“…We further confirmed the feasibility of using UQCRC2 as a stand-alone diagnostic biomarker for GC disease survival, wherein we found that the expression level of UQCRC2 showed a significant negative correlation with disease progression. (14).…”

Critical requirement of SOS1 RAS-GEF function for mitochondrial dynamics, metabolism, and redox homeostasis

“…complex I [46] and the UQCRC2 (Cytochrome b-c1 complex subunit 2) subunit of complex III [47], whereas no changes were detected in the level of the SDBH (Succinate dehydrogenase [ubiquinone] iron-sulfur subunit) of complex II [48], the COX IV (Cytochrome c oxidase subunit 4 isoform 1) subunit of complex IV [49], and the F1-beta-subunit of the mitochondrial ATP synthase of complex V [50] (Fig. 4A).…”

Mitochondrial Genetic and Epigenetic Regulations in Cancer: Therapeutic Potential

“…In contrast, osteosarcoma cell proliferation can be enhanced via targeting of ubiquinol-cytochrome c reductase core protein 1 (UQCRC1) with miR-214-3p [ 239 ]. In gastric cancer, the miR-370/UQCRC2 axis positively regulates the epithelial-mesenchymal transition (EMT) signalling that affects tumour proliferation and metastasis [ 240 ]. However, there is still limited information on direct regulation of mitochondria-encoded proteins by mitomiRs in cancer.…”