CircPUM1 Knockdown Confers Radiosensitivity in Oral Squamous Cell Carcinoma by Regulating the miR-580/STAT3 Pathway

Abstract

Background: CircPUM1 acts as an oncogene in a variety of tumors, and there is no related research on oral squamous cell carcinoma. This study aimed to evaluate the clinical significance of CircPUM1 in oral squamous cell carcinoma radiotherapy.Methods: Radio-resistant cell lines were established by increasing the X-ray dose. Analysis of CircPUM1 expression in oral squamous cell carcinoma was carried out using bioinformatics tools. Cell proliferation was analyzed with CCK-8 and colony formation. Protein and gene expressions were detected by Western blotting and qPCR. RNA interference inhibits endogenous gene expression. A luciferase reporter system and immunoprecipitation were used to validate the target of CircPUM1.Result: CircPUM1 was highly expressed in OSCC. The higher the expression level of CircPUM1 in OSCC, the worse the clinical features and prognosis. Knockdown of CircPUM1 enhances the sensitivity of OSCC cells to X-rays, and expression of exogenous CircPUM1 makes OSCC cells acquire radiation resistance. The absence of CircPUM1 blocked the cells in the G0/G1 phase and triggered apoptosis. The prediction of mir-580-binding site, luciferase reporter system, and immunoprecipitation confirmed that mir-580 is the binding site of CircPUM1. In addition, STAT3 was predicted and confirmed as the binding site of mir-580. Overexpression of STAT3 partially attenuated the radiosensitivity of OSCC cells to knockdown of CircPUM1.Conclusion: CircPUM1 has the oncogene expression profile in oral squamous cell carcinoma; patients with high expression of CircPUM1 have less benefit from radiotherapy and need more frequent follow-up. In addition, CircPUM1 may be a potential therapeutic target for oral squamous cell carcinoma. The CircPUM1/mir-580/STAT3 axis has a certain effect on the radiosensitivity of OSCC. These results suggest that patients with low expression of CircPUM1 may gain more benefits.

TXNL4B regulates radioresistance by controlling the PRP3‐mediated alternative splicing of FANCI

“… 46 STAT3β, one of the spliced isoforms of (Signal Transducer and Activator of Transcription 3) STAT3, serving as a dominant‐negative regulator, enhances sensitivity to radiotherapy 47 but STAT3 itself attenuates the radiosensitivity on the contrary. 48 Our study found that the alternative splicing of FANCI would produce two isoforms, of which one was showed aggravating lung cancer cells’ radioresistance, whereas another had no effects. Previous studies and our study demonstrate that while taking measures for the prevention and treatment of radioresistance, it should be paid more attention to the effects of alternative splice, which might offer a new and challenging approach to reverse therapeutic resistance.…”

“…Alternative splicing of coactivator‐associated arginine methyltransferase 1 (CARM1) by epithelial splicing regulatory protein 1 (ESRP1) resulted in lung cancer cells sensitize to chemotherapy 46 . STAT3β, one of the spliced isoforms of (Signal Transducer and Activator of Transcription 3) STAT3, serving as a dominant‐negative regulator, enhances sensitivity to radiotherapy 47 but STAT3 itself attenuates the radiosensitivity on the contrary 48 . Our study found that the alternative splicing of FANCI would produce two isoforms, of which one was showed aggravating lung cancer cells’ radioresistance, whereas another had no effects.…”

Network pharmacology and experiment validation investigate the potential mechanism of triptolide in oral squamous cell carcinoma

“…CCL4 enhances Angpt2 and VEGF-C expressions via the MEK/ERK/STAT3 and JAK2/STAT3 pathways, respectively, to promote angiogenesis and lymphangiogenesis in OSCC, thereby increasing the propensity of metastasis ( Lien et al, 2018 ; Lu et al, 2022 ). Additionally, STAT3 is associated with the chemosensitivity and radiosensitivity of OSCC cells ( Chen et al, 2019 ; Jia et al, 2022 ). Fewer studies have been conducted on the association between STAT1 and OSCC than on the role of STAT3 in OSCC.…”