<p>Mechanism of the Regulatory Effect of Overexpression of circMTO1 on Proliferation and Apoptosis of Hepatoma Cells via miR-9-5p/NOX4 Axis</p>

Abstract

To investigate the potential role of the circMTO1/miR-9-5p/NOX4 axis in liver cancer. Materials and Methods: Human genome-wide circrna microarray V2 was used for analyzing the expression profile of circRNAs in human tissue samples. The TargetScan database was used to predict target genes. Gene overexpression and silencing in hepatoma cell lines were achieved by transfecting the cells with suitable constructs. Quantitative real time PCR and Western blotting were used to analyze gene and protein expression levels. CCK-8 analysis was performed to detect cell proliferation and the transwell assay for analyzing cell migration. Annexin V-FITC/PI staining and immunohistochemistry were respectively used to detect apoptosis and protein expression. Results: CircMTO1 were down-regulated in the liver cancer tissues and cell lines compared to their respective normal controls. TargetScan database screening and dual luciferase assay revealed that circMTO1 was a molecular sponge of miR-9-5p, and NOX4 was the target gene of miR-9-5p. Overexpression of circMTO1 and NOX4 inhibited proliferation and migration of hepatoma cells, while the overexpression of miR-9-5p had the opposite effects. In contrast, overexpression of circMTO1 and NOX4 promoted apoptosis, while that of miR-9-5p decreased the cell apoptosis rates. Conclusion: Overexpression of CircMTO1 acts as tumor suppressor in liver cancer by sponging miR-9-5p, which upregulates NOX4.

circMTO1 sponges microRNA‑219a‑5p to enhance gallbladder cancer progression via the TGF‑β/Smad and EGFR pathways

“…Consistent with these findings, the results of the present study demonstrated that circMTO1 knockdown decreased cell viability and tube formation of HDLECs, while promoting the apoptosis of GBC cells. Notably, a few studies have reported that overexpression of circMTO1 enhances the apoptosis of gastric cancer cells and hepatoma cells (8,29). These findings oppose the results of the present study, thus it was hypothesized that circMTO1 may exert different roles in different types of cancer.…”

The Roles of circMTO1 in Cancer

“…With advancement of circRNA research, differences in circMTO1 expression have been detected in normal and diseased tissue. Many studies have verified that circMTO1 is abnormally expressed in a large number of tumors, including rectal cancer, osteosarcoma, glioblastoma, cervical cancer, gallbladder cancer, gastric carcinoma, lung adenocarcinoma, ovarian cancer, hepatocellular carcinoma, renal cell carcinoma, prostate cancer, bladder cancer, colorectal cancer, and breast cancer ( Han et al, 2017 ; Liu et al, 2018 ; Rao et al, 2018 ; Chen M. et al, 2019 ; Fan et al, 2019 ; Li Y. et al, 2019 ; Zhang B. et al, 2019 ; Hu and Guo, 2020 ; Hu et al, 2020 ; Li K. et al, 2020 ; Li L. et al, 2020 ; Liu et al, 2021 ; Song et al, 2020 ; Wang J. et al, 2020 ; Wang N. et al, 2020 ; Wang X. et al, 2020 ). Furthermore, upregulation of circMTO1 expression was reported to inhibit cell proliferation in rectal cancer, osteosarcoma, glioblastoma, gastric carcinoma, lung adenocarcinoma, ovarian cancer, renal cell carcinoma, hepatocellular carcinoma, prostate cancer, colorectal cancer, and breast cancer.…”

“… Han et al (2017) found that circMTO1 could act as a sponge of the oncogenic miR-9 to promote the expression of p21, thereby inhibiting cell proliferation and invasion of HCC cells. In addition, Wang X. et al (2020) also found that overexpression of circMTO1 could upregulate NADPH oxidase 4 (NOX4) expression by sponging miR-9-5p, thereby promoting apoptosis ( Han et al, 2017 ; Wang J. et al, 2020 ). Overall, these results suggest that reduced expression of circMTO1 may be a prognostic biomarker, as well as a potential therapeutic target for the treatment of HCC.…”

CircRNAs: a new target for the diagnosis and treatment of digestive system neoplasms

“…For example, circMTO1, which is significantly downregulated in HC, can be used as a sponge for miR-9 to promote the expression of P21 and to inhibit the proliferation and invasion of HC 76 . Additionally, Wang et al found that circMTO1 can also exert its inhibitory effect through the miR-9-5p/NOX4 axis 77 . In addition, circRNA-5692 is expressed at low levels in HCC.…”