LINC00460 knockdown sensitizes cervical cancer to cisplatin by downregulating TGFBI.

Ping Tian, Yuanyuan Feng, Ling Tao

Chemical biology & drug design 2024 Jan

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The acquired resistance of cancer to cisplatin (DDP) limits the efficacy of chemotherapy. The prognostic value of long noncoding RNA (lncRNA) LINC00460 has been reported in cervical cancer. However, its effect on DDP sensitivity in cervical cancer remains poorly understood. In present study, LINC00460 was screened out through bioinformatics analysis. The expression levels of mRNAs and proteins were measured by reverse transcription-quantitative PCR (RT-qPCR) or western blot analysis. The sensitivity to DDP was investigated using an CCK8 assay. Cell apoptosis was determined by flow cytometry. The differentially expressed genes that were associated with the poor prognosis of cervical cancer were screened, and their correlations with LINC00460 expression were explored using Pearson's correlation analysis. Tumor xenograft model was used to assess the effect of LINC00460 knockdown on DDP sensitivity in vivo. The interaction between miR-338-3p and LINC00460 or transforming growth factor β-induced protein (TGFBI) was confirmed by RNA immunoprecipitation (RIP) and luciferase reporter assays. LINC00460 expression was increased in cervical cancer tissues and cells. High expression of LINC00460 was associated with dismal prognosis in cervical cancer patients. Silencing of LINC00460 increased drug sensitivity and induced apoptosis in DDP-resistant-cervical cancer cells. LINC00460 knockdown enhanced DDP sensitivity in cervical cancer cells largely by downregulating TGFBI expression. LINC00460 knockdown enhanced the sensitivity of cervical cancer to DDP in vivo, and this effect was partly mediated by the downregulation of TGFBI. LINC00460 positively regulated TGFBI expression, possibly by acting as a sponge of miR-338-3p. LINC00460 knockdown contributed to DDP sensitivity of cervical cancer by downregulating TGFBI, providing a novel mechanism underlying the acquisition of DDP sensitivity. © 2023 John Wiley & Sons Ltd.

Citation

Ping Tian, Yuanyuan Feng, Ling Tao. LINC00460 knockdown sensitizes cervical cancer to cisplatin by downregulating TGFBI. Chemical biology & drug design. 2024 Jan;103(1):e14424