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Research Sheds Light on Molecular Mechanisms of Cisplatin-Resistant Bladder Cancer

By: Jenna Carter, PhD
Posted: Friday, July 15, 2022

Studies have shown that cisplatin resistance limits favorable therapeutic outcomes in many patients with bladder cancer who receive this drug. Since cisplatin is a key treatment of bladder cancer, Chinese researchers investigated the critical molecular targets involved in cisplatin resistance. Peng Deng, MD, of the China Medical University, Shenyang, and colleagues identified a type of bladder cancer–induced circular RNA (circ_0058063) and performed various loss-of-function experiments to assess its role in cisplatin resistance. This work was published in BMC Cancer. The findings revealed that downregulation of circ_0058063 suppressed cell proliferation and tumor growth as well as induced apoptosis in cisplatin-resistant bladder cancer cells.

“Drug resistance to [cisplatin] seriously limits the therapeutic efficacy of this chemical drug for the treatment of [bladder cancer]. Also, as the results of its unclear molecular mechanisms, there are still no effective adjuvant therapy strategies to improve [cisplatin] sensitivity. Therefore, it is very important to clarify the molecular mechanism involved in the…chemoresistance of [bladder cancer] cells, which is beneficial to the development of effective chemotherapeutics…,” stated Dr. Deng and colleagues.

Bladder cancer specimens were collected from patients undergoing cystectomy between August 2019 and February 2020 at the Shengjing Hospital of the China Medical University. Patient samples were then divided into the resistant group (n = 16) and the sensitive group (n = 19), according to standard cisplatin responses published elsewhere. A series of molecular assays, cell cultures, and genetic experiments were then conducted.

The findings revealed that circ_0058063 was overexpressed in cisplatin-resistant tissue and cells compared with their cisplatin-sensitive counterparts (P < .05). Loss-of-function experiments validated that downregulation of circ_0058063 rescued cell viability and increased apoptosis in cisplatin-resistant cells (P < .05). Knockdown experiments also revealed suppression of cell proliferation and tumor growth in cisplatin-resistant cells both in vitro and in vivo. Further experiments revealed that circ_0058063 may act as a sponge for miR-335-5p and positively regulate B2M expression.

Disclosure: The study authors reported no conflicts of interest.


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