Hsa_circ_001680 affects the proliferation and migration of CRC and mediates its chemoresistance by regulating BMI1 through miR-340

Abstract

Background: Accumulating evidence indicates that circular RNAs (circRNAs) act as microRNA (miRNA) sponges to directly inhibit specific miRNAs and alter their ability to regulate gene expression at the post-transcriptional level; this mechanism is believed to occur in various cancers. However, the expression level, precise function and mechanism of circ_001680 in colorectal carcinoma (CRC) are largely unknown. Methods: qRT-PCR was used to detect the expression of circ_001680 and miR-340 in human CRC tissues and their matched normal tissues. Bioinformatics analyses and dual-fluorescence reporter assays were used to evaluate whether circ_001680 could bind to miR-340. Circ_001680 overexpression and knockdown cell lines were constructed to investigate the proliferation and migration abilities in vivo and in vitro through function-based experiments, including CCK8, plate clone formation, transwell, and wounding healing assays. The relationships among circ_001680, miR-340 and BMI1 were investigated by bioinformatics analyses, dual-fluorescence reporter system, FISH, RIP and RNA pull down assays. Sphere forming assays and flow cytometry analyses were used to assess the effect of circ_001680 on the stemness characteristics of CRC cells. Results: Circ_001680 was more highly expressed in of CRC tissue than in matched adjacent normal tissues from the same patients. Circ_001680 was observed to enhance the proliferation and migration capacity of CRC cells. Furthermore, dual-fluorescence reporter assays confirmed that circ_001680 affects the expression of BMI1 by targeting miR-340. More importantly, we also found that circ_001680 could promote the cancer stem cell (CSC) population in CRC and induce irinotecan therapeutic resistance by regulating the miR-340 target gene BMI1. Conclusions: Our results demonstrated that circ_001680 is a part of a novel strategy to induce chemotherapy resistance in CRC through BMI1 upregulation. Moreover, circ_001680 may be a promising diagnostic and prognostic marker to determine the success of irinotecan-based chemotherapy.

The U2AF2 /circRNA ARF1/miR-342–3p/ISL2 feedback loop regulates angiogenesis in glioma stem cells

“…Circular RNAs (circRNAs) have emerged as a new class of noncoding RNAs that form single-stranded closed loop structures by forming covalent bonds without the 5′ caps and 3′ poly(A) tails [16]. The circular structure of circRNAs facilitates their stable existence in different tissues, and their ability to play vital roles in multiple biological functions [17].…”

<p>Circular RNA CircPRMT5 Accelerates Proliferation and Invasion of Papillary Thyroid Cancer Through Regulation of miR-30c/E2F3 Axis</p>

“…10 In addition, hsa_circ_001680 regulates growth and metastasis in colorectal cancer cells and affects chemoresistance through miR-340/BMI1 axis. 11 However, how circRNA dysregulation affects PTC development remains undefined.…”

Functions and mechanisms of circular RNAs in cancer radiotherapy and chemotherapy resistance

“…Circ_001680 is increased in CRC tissues. In addition to enhancing proliferation and migration, it also triggers irinotecan resistance via sponging miR-340 to reduce BMI1 transcription, which supports the population of CSCs [46].…”

“…Circ_001680 and circ-NOTCH1 are increased in colorectal cancer (CRC) and gastric cancer (GC), respectively. Both promote the cancer stem cell (CSC) population in cancer [46,47]. Failing to eradicate cancer cells that acquire stemness via activation of EMT or senescence is another reason for compromised therapy outcomes in cancer [48][49][50][51].…”