Circular RNA Cdr1as sensitizes bladder cancer to cisplatin by upregulating APAF1 expression through miR‐1270 inhibition

Abstract

Circular RNAs (circRNAs) have recently emerged as essential regulators in carcinogenesis and cancer progression. Previous studies have shown that Cdr1as functions as a microRNA (miRNA) sponge in various cancer types. However, the role of Cdr1as in cisplatin chemosensitivity in bladder cancer remains unclear. Here, we used real‐time PCR to examine miRNA and gene expression in bladder cancer tissues and cell lines. The abilities of Cdr1as and its downstream regulatory molecules to induce apoptosis and promote cisplatin‐induced chemosensitivity of bladder cancer cells were determined by flow cytometry and cell counting kit. Bioinformatic analysis was utilized to predict potential miRNA target sites, and biotin‐coupled miRNA capture, biotin‐coupled probe pull‐down assay, and RNA fluorescent in situ hybridization were used to study the interaction between Cdr1as and target miRNAs. Dual‐luciferase reporter assay was also used to validate the target genes of miRNAs. The expression level of apoptotic protease‐activating factor 1 (APAF1) in bladder cancer cells was identified via western blot. Finally, the sensitivity of Cdr1as to cisplatin chemotherapy in nude mice xenografts was evaluated in terms of the size, volume of tumors, and the survival of mice. We report that Cdr1as induced the apoptosis and enhanced the cisplatin chemosensitivity of bladder cancer cells both in vitro and in vivo . Silencing of APAF1 reduced the sensitivity of bladder cancer cells to cisplatin chemotherapy. Furthermore, Cdr1as could directly sponge miR‐1270 and abolish its effect on APAF1. Our study verified that Cdr1as exerts a cisplatin‐chemosensitization effect on bladder cancer cells through the Cdr1as/miR‐1270/APAF1 axis. This newly identified axis may be a potential therapeutic target for bladder cancer patients.

CircRNA CDR1as knockdown inhibits progression of non‐small‐cell lung cancer by regulating miR‐219a‐5p/SOX5 axis

“…CircRNAs may serve as ceRNAs or sponges for miRNAs to participate in the development of cancers . Several reports have documented that circCDR1as could act as a ceRNA to regulate the processes of tumor cells . In the present study, we confirmed circCDR1as as a sponge of miR‐219a‐5p by dual‐luciferase reporter assay.…”

“…32 Several reports have documented that circCDR1as could act as a ceRNA to regulate the processes of tumor cells. 33,34 In the present study, we confirmed circCDR1as as a sponge of miR-219a-5p by dual-luciferase reporter assay. Moreover, we found that miR-219a-5p expression declined in NSCLC and its overexpression repressed NSCLC development in vitro, which was also in agreement with previous studies.…”

Circular RNA-CDR1as acts as the sponge of microRNA-641 to promote osteoarthritis progression

“…CircRNA-CDR1as is known to act as sponge of multiple miRNAs. Besides miR-7, which has more than 70 binding sites in circRNA-CDR1as, circRNA-CDR1as has been reported to be sponge for miR-135a [31], MiR-1270 [26], and miR135b-5p [27]. In this study, we further expanded the family of its target miRNAs.…”

“…Much of the research on OA has focused on its diagnosis, pathogenesis, epigenetic regulation, and potential therapeutic purposes containing microRNAs. With the identification and further functional analysis of circRNA-CDR1as, its function as a sponge for multiple miRNAs has been revealed [14,[22][23][24][25][26][27][28]. But its role in OA development has not been explored previously.…”

“…It is reported that circRNA-CDR1as contains about 70 conserved binding sites for miR-7 [22], which is involved in the progress of cancers [23], Alzheimer's disease [20], insulin secretion [18], myocardial Infarction [24] and osteoblastic differentiation of stem cells [25] by regulation various signaling pathways. CircRNA-CDR1as also contains binding sites for other micoRNAs and functions as their sponges [26,27], including those known to play critical roles in bone development and chondrogenesis [17]. MiR-641 has been shown to be downregulated in osteoarthritic human chondrocytes [28], but its regulation and function in OA has not been reported.…”