Silencing CDR1as inhibits colorectal cancer progression through regulating microRNA-7

Abstract

An increasing number of studies have demonstrated that circular RNAs (circRNAs) can regulate gene expression through interacting with microRNAs. In this study, we analyzed the expression of antisense to CDR1as in colorectal cancer (CRC). CDR1as had a higher expression in CRC tissues compared to adjacent, normal mucosa and was positively associated with tumor size, T stage, lymph node metastasis, and poor overall survival (OS). Downregulation of CDR1as suppressed CRC cell proliferation and invasion and increased microRNA-7 (miR-7) expression. Intriguingly, ectopic expression of miR-7 in CRC cells consistently inhibited proliferation and invasion, and the miR-7 inhibitor was able to rescue the function of CDR1as knockdown. Mechanistic studies demonstrated that CDR1as silencing suppressed EGFR and IGF-1R expression, which could be partially blocked by the miR-7 inhibitor. Finally, positive correlations between CDR1as expression and EGFR and IGF-1R expression were observed in CRC samples. Thus, given the importance of CDR1as in blocking miR-7 and positively regulating EGFR and IGF-1R, dysregulated CDR1as expression may play an important role in CRC progression.

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

“…Dysregulated circRNAs may be associated with the diagnosis and therapy of cancers . Several reports have demonstrated that circCDR1as could function as an oncogenic circRNA or tumor suppressor in different cancers because of the change of tumor microenvironment . Zhang et al .…”

“…Furthermore, emerging evidence suggests that several circRNAs might contribute to the progression of NSCLC . Accruing evidence demonstrates that circRNA antisense to cerebellar degeneration‐related protein 1 transcript (circCDR1as) could promote the development of hepatocellular carcinoma, colorectal cancer and laryngeal squamous cell carcinoma and inhibit the progression of bladder cancer and ovarian cancer . Importantly, a previous study reveals that circCDR1as acts as an oncogene to facilitate the development of NSCLC .…”

“…[8][9][10] Accruing evidence demonstrates that circRNA antisense to cerebellar degeneration-related protein 1 transcript (circCDR1as) could promote the development of hepatocellular carcinoma, colorectal cancer and laryngeal squamous cell carcinoma and inhibit the progression of bladder cancer and ovarian cancer. [11][12][13][14][15] Importantly, a previous study reveals that circCDR1as acts as an oncogene to facilitate the development of NSCLC. 16 However, the mechanism underlying the participation of circCDR1as in the progression of NSCLC remains unclear.…”

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

“…It was found that Cdr1as can sponge miR‐7 and regulate downstream target gene expression (Memczak et al , ). Other studies have shown that Cdr1as plays oncogenic roles in many tumors, such as hepatocellular carcinoma (Yu et al , ) and colorectal cancer (Tang et al , ). In our previous study (Li et al , ), however, we found that Cdr1as sponges miR‐135a instead of miR‐7, restores p21 activity, and mediates cell cycle arrest in bladder cancer cells.…”

A circular twist on microRNA regulation

“…A further layer of regulation is offered by miR-671, which is able to trigger Cdr1as degradation, and as an indirect consequence, to affect miR-7 levels [6]. Knockdown of CDR1as in colorectal cancer and hepatocellular carcinoma cell lines resulted in decreased tumor proliferation, increased miR-7 levels, and downregulation of miR-7 targets [8,9]. It is important to note that all these studies exploited shRNAs and siRNAs to target circRNAs.…”