Circular RNA hsa_circRNA_102209 promotes the growth and metastasis of colorectal cancer through miR-761-mediated Ras and Rab interactor 1 signaling

Abstract

In our study, has_circRNA_102209 was the most elevated regulator in colorectal cancer (CRC) tissues according to circRNA array data. The levels of hsa_circRNA_102209 in CRC specimens and cells, as well as its effects on CRC cells were investigated. The expression of hsa_circRNA_102209 in CRC and paired non-cancerous samples, human CRC, and normal colonic epithelial cells were examined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cells with hsa_circRNA_102209 knockdown were established using lentiviral vectors. Cell proliferative ability was evaluated using CCK-8 assay; cell migrative/invasive activities were determined using wound healing/Transwell assay. Cell cycle arrest and apoptosis were assessed by flow cytometry; apoptosis, and EMT markers were examined using RT-qPCR and western blotting. Tumor development and levels of associated proteins were determined in hsa_circRNA_102209 knockdown mice. Our results revealed that expression of hsa_circRNA_102209 was remarkably increased in CRC tissues, where the levels of miR-761 were notably reduced (P < .05). Additionally, the levels of hsa_circRNA_102209 were associated with histology grade and occurrence of liver metastasis in CRC patients, and the expression of hsa_circRNA_102209 and miR-761 were negatively correlated (P < .05). Moreover, hsa_circRNA_102209 was upregulated in CRC cells compared with normal colonic epithelial cells. Knockdown of hsa_circRNA_102209 notably inhibited the proliferation, migration, invasion, and EMT of CRC cells (P < .05), whereas cell cycle arrest at G0/G1 phase and apoptosis were enhanced (P < .05). Furthermore, miR-761/Ras and Rab interactor 1 (RIN1) axis was the putative target of hsa_circRNA_102209 in CRC and involved in hsa_circRNA_102209-modulated growth and metastasis of CRC cells (P < .05). Knockdown of hsa_circRNA_102209 also remarkably suppressed tumor growth in vivo (P < .05). In summary, our data revealed that the expression of hsa_circRNA_102209 was elevated in CRC samples and cells. Furthermore, hsa_circRNA_102209 could promote the progression of CRC through miR-761/RIN1 axis. More importantly, hsa_circRNA_102209/miR-761/RIN1 signaling may be a novel therapeutic target for the treatment of CRC patients.

Keywords: RIN1 signaling; colorectal cancer; growth; hsa_circRNA_102209; metastasis.