Circ_0078767 Inhibits the Progression of Non-Small-Cell Lung Cancer by Regulating the GPX3 Expression by Adsorbing miR-665

Abstract

Non-small-cell lung cancer (NSCLC) is one of the most serious cancers. The circular RNA_0078767 (circ_0078767) expression was decreased in NSCLC tissues. However, the molecular mechanism of circ_0078767 remains unknown. The expression of circ_0078767, microRNA-665 (miR-665), and glutathione peroxidase 3 (GPX3) was detected by quantitative real-time fluorescence polymerase chain reaction (qRT-PCR). Cell proliferation, migration, and invasion were detected by colony formation assay and transwell assay, respectively. The lactate production and glucose consumption were tested by glycolysis. Western blot examined the protein levels of hexokinase-2 (HK2), matrix metalloproteinase-9 (MMP9), and GPX3 cells. Circinteractome predicted the relationship between miR-665 and circ_0078767 or GPX3 and was verified by dual luciferase reporter assays. The xenotransplantation model was established to study the role of circ_0078767 in vivo. The expression of circ_0078767 and GPX3 was decreased in NSCLC tissues, while the expression of miR-665 was increased. Circ_0078767 can sponge miR-665, and GPX3 is the target of miR-665. In vitro complement experiments showed that knockdown of circ_0078767 significantly promoted malignant behavior of NSCLC, while cotransfection of miR-665 inhibitor partially reduced this change. In addition, the GPX3 overexpression decreased the promoting effects of miR-665 upregulation on proliferation, migration, and invasion of NSCLC cells. Mechanically, circ_0078767 regulates the GPX3 expression in NSCLC cells by spongy miR-665. In addition, in vivo studies have shown that downregulation of circ_0078767 promotes tumor growth. Circ_0078767 silencing promotes proliferation, migration, invasion, and glycolysis of NSCLC cells by regulating the miR-665/GPX3 axis, suggesting that circ_0078767/miR-665/GPX3 axis may be a potential regulatory mechanism for the treatment of NSCLC.

Molecular mechanisms and prognostic value of the selenoprotein gene family in lung adenocarcinoma and lung squamous cell carcinoma

“…Several studies have indicated that GPX3 plays a tumor-suppressive role in NSCLC by repressing tumor cell proliferation, migration, and invasion. For instance, downregulation of miR-196a could upregulate GPX3, which results in inactivation of the c-Jun N-terminal kinase (JNK) signaling pathway, leading to a decline in stemness, self-renewal capacity, and tumorigenicity of NSCLC [48]; a high expression of GPX3 could inhibit the malignant biological behaviors of NSCLC cells by modulating the miR-665/GPX3 signaling pathways [49], and overexpression of GPX3 could signi cantly inactivate reactive oxygen species, thereby repressing the Erk-NF-κB-cyclin B1 signaling pathway and causing cell cycle arrest [50]. However, interestingly, polarized alveolar type 2 epithelial cells highly expressed GPX3 and abundantly produced interleukin-10, thus inhibiting CD4 + T cell proliferation and enhancing regulatory T cell generation, eventually leading to the formation of a premetastatic niche required for metastasis [51].…”

Transcriptome analysis of hepatic fibrosis induced by common bile duct ligation

“…Glutathione peroxidase 3 (Gpx3) is an antioxidant enzyme, the only exocrine form of glutathione peroxidase family, which acts in detoxi cation of hydrogen peroxide to shields cells and enzymes from oxidative damage and regulates redox 19 . Besides, as a tumor suppressor gene, Gpx3 is involved in the occurrence of a variety of cancer diseases 20 , including ovarian cancer, breast cancer 21 , thyroid cancer 22 and lung cancer 23 . Furthermore, Gpx3 is also a tumor suppressor gene in HCC.…”

Circ_0087378 intensifies the malignant behavior of non-small cell lung cancer cells in vitro by facilitating DDR1 via sponging miR-199a-5p

“…Famously, circRNAs can participate in the post-transcriptional regulation of coding gene expression in cancer by acting as microRNA (miRNA) sponges ( 8 ). The significance of circRNAs in the pathogenesis of NSCLC has been established ( 9 , 10 ). CircRNA (circ)_0087378 has been recently identified to be down-regulated in breast cancer; it suppressed the progression of breast cancer by elevating secreted frizzled related protein-1 (SFRP1) expression via sponging miRNA (miR)-1260b ( 11 ).…”