Hsa_circRNA_101036 acts as tumor-suppressor in oral squamous cell carcinoma cells via inducing endoplasmic reticulum stress

W. Deng, J. Fu, T. Wang, J.-X. Chen, L.-B. Fu, W. Peng

Department of Oral and Maxillofacial Surgery, Hainan General Hospital, Haikou, Hainan, China. drpengwei@yeah.net

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• Oncology

OBJECTIVE: Endoplasmic reticulum (ER) stress has an effect on cancer cell proliferation and survival. TMTC1 has been reported to be involved in cell proliferation and inflammation, and development of ER. Hsa_circRNA_101036 is an exon circRNA formed by splicing of TMTC1 mRNA precursor. This study intends to explore the effect of hsa_circRNA_101036 on the malignant behavior of oral squamous cell carcinoma through endoplasmic reticulum stress.

MATERIALS AND METHODS: We firstly evaluated the levels of Hsa_circRNA_101036 in human oral mucous fibroblasts (hOMF), and in several OSCC cell lines, including FaDu, OECM1, SAS, HSC3. Then, we studied the effects of overexpression of Hsa_circRNA_101036 on the cell proliferation, apoptosis, invasion, migration, and cytokine release in OSCC cells. Finally, we evaluated the levels of CHOP that are critical in ER and the ROS levels in OSCC cells.

RESULTS: We found that compared with hOMF, a significantly lower mRNA expression of Hsa_circRNA_101036 was found in OECM1 and HSC3 cells. In OECM1 and HSC3 cells, with overexpression of Hsa_circRNA_101036, a significant decrease in cell proliferation, apoptosis, invasion, migration, and cytokine release was found. A significantly increased ROS, as well as increased protein level of CHOP, P38 and Bcl-2, was found in cells with Hsa_circRNA_101036 overexpression.

CONCLUSIONS: This study indicated that Hsa_circRNA_101036 may acts as a tumor suppressor in OSCC via regulating the ER in cancer cells.

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