Overexpressed circ-CEP128, a potential new circular RNA biomarker, promotes cisplatin resistance of bladder cancer cells by regulating necroptosis

Abstract Background Bladder cancer (BC) is the most common malignancy of urinary system and cisplatin (DDP) remains the only chemotherapy option for treatment of BC at the advanced stage. The critical molecules involved in the regulation of cisplatin resistance are still largely unknown. CircRNAs has been demonstrated to be involved in tumorigenesis and development and drug resistance of various cancer cells. CircCEP128 contributed to BC progression by regulating miR-145-5p/MYD88/MAKP axis. However, functions and molecular mechanisms of circCEP128 in DDP resistance of bladder cancer cells still remain largely unclear. Methods Bladder cancer tissue and the corresponding adjacent normal tissue as well as serum samples were obtained from a total of 60 BC patients who received the same cisplatin-based chemotherapy. The expression level of circCEP128 in tissues and serums was measured using qRT-PCR. WB was utilized to detect expression level of PCNA, Cyclin D1, RIPK3, p-RIPK3, MLKL or p-MLKL. Functionally, BC cell viability and proliferation are measured through relevant experiments, including CCK8 assay and cell colony formation assay. Results In the current study, we demonstrated that circCEP128 expression was distinctly elevated in the BC tissues and serums, especially in the chemoresistant BC tissues or cell lines, correlated with poor prognosis of BC patients. In addition, ROC curve suggested that circCEP128 might serve as an effective diagnostic biomarker for BC and treatment. Furthermore, cell function assays showed that circCEP128 silencing by siRNA could reverse the drug-resistance of BC cells to cisplatin by inducing necroptosis through regulation of RIPK3/MLKL signaling pathway. Conclusions Our findings indicated that circCEP128 may serve as a valuable diagnostic biomarker in BC and contribute to cisplatin resistance of bladder cancer cells by repressing necroptosis through RIPK3/MLKL signaling pathway. These findings provide novel insights into the role of circCEP128 as a biomarker for the diagnosis and treatment target of BC.

Download Full-text

LncRNA-MALAT1 mediates cisplatin resistance via miR-101-3p/VEGF-C pathway in bladder cancer

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gmz112 ◽

2019 ◽

Cited By ~ 4

Author(s):

Peihua Liu ◽

Xiaozhou Li ◽

Yu Cui ◽

Jinbo Chen ◽

Chao Li ◽

...

Keyword(s):

Drug Resistance ◽

Bladder Cancer ◽

Cancer Cells ◽

Drug Sensitivity ◽

Molecular Mechanisms ◽

Cisplatin Resistance ◽

Chemotherapeutic Drug ◽

Lncrna Malat1 ◽

Immortalized Cells ◽

Standard Strategy

Abstract Cisplatin (CDDP)-based chemotherapy is a standard strategy for the clinical treatment of patients with bladder cancer (BC). However, the anti-tumor efficacy of cisplatin is affected by multiple chemoresistance with complex molecular mechanisms. Recent evidence highlights the crucial regulatory roles of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in the progression of cancers and development of drug resistance. However, the roles and underlying molecular mechanisms of MALAT1 in cisplatin resistance of the BC cells remain largely unclear. In this study, we firstly demonstrated that MALAT1 expression was up-regulated in the BC tissues compared to the normal adjacent tissues and elevated in the cancer cells compared to the epithelial immortalized cells. Secondly, we found that suppression of MALAT1 enhanced the chemotherapeutic drug sensitivity and inhibited the cisplatin resistance of the BC cells. Thirdly, we showed that MALAT1 affected the cisplatin resistance of the BC cells via regulating the miR-101-3p/VEGF-C pathway. In summary, this study demonstrates that MALAT1, miR-101-3p and VEGF-C form a regulatory axis to affect the chemo-resistance of BC cells to CDDP, and provides novel potential targets for treatment of BC.

Download Full-text