Long Non-Coding RNA DIO3OS Binds to microRNA-130b to Restore Radiosensitivity in Esophageal Squamous Cell Carcinoma by Upregulating PAX9

Abstract

Background: Esophageal squamous cell carcinoma (ESCC) ranks as one of the most fatal cancers worldwide for its aggression and unsatisfactory survival rate. The long non-coding RNA (lncRNA)-microRNA (miRNA)-mRNA axis has been highlighted as a potency biomarker for enhancing the radiosensitivity of ESCC. Hence, we investigated the functional mechanism of the DIO3OS/miR-130b/paired box 9 (PAX9) axis in the radioresistance of ESCC cells. Methods: In cell experiments, we altered the miR-130b expression in ESCC cells using mimics or inhibitors to examine its effects on ESCC cell activities in response to 4 Gy irradiation, as well as the involvement of DIO3OS and PAX9. Tumor xenograft experiments were then conducted to observe the effect of miR-130b, DIO3OS and PAX9 on radiosensitivity of ESCC ells in vivo. Results: miR-130b was found to be highly-expressed in the ESCC. Downregulated miR-130b inhibited proliferation, invasion and resistance to apoptosis in ESCC cells. DIO3OS and PAX9 were reduced in ESCC. A notable finding revealed that miR-130b could bind to DIO3OS and PAX9 respectively. DIO3OS could upregulate PAX9 by binding to miR-130b, which ultimately promoted the radiosensitivity of ESCC in vitro and in vivo. Conclusion: Taken together, DIO3OS upregulates the expression of PAX9 by binding to miR-130b, ultimately promoting the radiosensitivity of ESCC.

Methylation of N6 adenosine‐related long noncoding RNA: effects on prognosis and treatment in ‘driver‐gene‐negative’ lung adenocarcinoma

“…DIO3OS may be the most important key m6AlncRNA in the development of many cancers. Many studies have shown that low DIO3OS expression promotes the occurrence and progression of cancers such as hepatocellular carcinoma, pancreatic carcinoma, and esophageal squamous cell carcinoma [37,39,50,51]. A recent study also suggested that CpG456 methylation downregulated DIO3OS expression leading to tumorigenesis and metastasis in NSCLC, which indicates that it might exhibit the similar CpG456 methylation in ‘driver‐gene‐negative’ LUAD [52].…”