The CircRNA-ACAP2/Hsa-miR-21-5p/ Tiam1 Regulatory Feedback Circuit Affects the Proliferation, Migration, and Invasion of Colon Cancer SW480 Cells

Abstract

Background/Aims: Circular RNAs (circRNAs), a type of RNA that is widely expressed in human cells, have essential roles in the development and progression of cancer. CircRNAs contain microRNA (miRNA) binding sites and can function as miRNA sponges to regulate gene expression by removing the inhibitory effect of an miRNA on its target gene. Methods: We used the bioinformatics software TargetScan and miRanda to predict circRNA-miRNA and miRNAi-Mrna interactions. Rate of inhibiting of proliferation was measured using a WST-8 cell proliferation assay. Clone formation ability was assessed with a clone formation inhibition test. Cell invasion and migration capacity was evaluated by performing a Transwell assay. Relative gene expression was assessed using quantitative real-time polymerase chain reaction and relative protein expression levels were determined with western blotting. circRNA and miRNA interaction was confirmed by dual-luciferase reporter and RNA-pull down assays. Results: In the present study, the miRNA hsa-miR-21-5p was a target of circRNA-ACAP2, and T lymphoma invasion and metastasis protein 1 (Tiam1) was identified as a target gene of hsa-miR-21-5p. CircRNA-ACAP2 and Tiam1 were shown to be highly expressed in colon cancer tissue and colon cancer SW480 cells, but miR-21-5p was expressed at a low level. SW480 cell proliferation was suppressed when the expression of circRNA-ACAP2 and Tiam1 was decreased and the expression of miR-21-5p was increased in vivo and in vitro. SW480 cell migration and invasion were also inhibited under the same circumstance. The circRNA-ACAP2 interaction regulated the expression of miR-21-5p, and miR-21-5p regulated the expression of Tiam1. Down-regulation of circRNA-ACAP2 promoted miR-21-5p expression, which further suppressed the transcription and translation of Tiam1. Conclusion: The present study shows that the circRNA-ACAP2/hsa-miR-21-5p/Tiam1 regulatory feedback circuit could affect the proliferation, migration, and invasion of colon cancer SW480 cells. This was probably due to the fact that circRNA-ACAP2 could act as a miRNA sponge to regulate Tiam1 expression by removing the inhibitory effect of miR-21-5p on Tiam1 expression. The results from this study have revealed new insights into the pathogenicity of colon cancer and may provide novel therapeutic targets for the treatment of colon cancer.

Extracellular nanovesicles‐transmitted circular RNA has_circ_0000190 suppresses osteosarcoma progression

“…Accumulating evidence has shown that various biochemical cellular processes including proliferation and migration are under the control of circRNAs. 26 Based on the obtained results, the putative tumour suppressor function of circ-0000190 in human osteosarcoma cells was examined. Numerous assays we conducted revealed that overexpression of circ-0000190 weakened cell proliferation, migration and invasion.…”

circEPSTI1 regulates ovarian cancer progression via decoying miR‐942

“…13 In colon cancer, circRNA-ACAP2 sponges miR-21-5p to regulate cell proliferation, migration and invasion. 14 In ovarian cancer, hsa_circ_0061140 affects cell growth and metastasis through sponging miR-370. 15 Here, we found that circEPSTI1 could bind to miR-942 and acted as a miRNA sponge.…”

The Regulatory Functions of Circular RNAs in Digestive System Cancers

“…Six circRNAs have been found to be upregulated during the progression of CRC, and knockdown of circCCDC66 [46], circRNA-ACAP2 [47], and hsa_circ_0000069 [48] notably restrained CRC cell migration, invasion, and proliferation. In addition, circ-BANP [49] and hsa_circ_0007534 [50] participate in the regulation of CRC cell proliferation.…”

“…In addition, circ-BANP [49] and hsa_circ_0007534 [50] participate in the regulation of CRC cell proliferation. Among these six circRNAs, circCCDC66 [46], circRNA-ACAP2 [47], and hsa_circ_0020397 [51] could be miRNA sponges that regulate the expression level of their targets.…”

“…The circRNA circCCDC66 was found to serve as a miRNA sponge to protect MYC mRNA from attack through miR-93 and miRNA-33b [46]. CircRNA-ACAP2 acted as a miRNA sponge to increase the expression of T lymphoma invasion and metastasis protein 1 (Tiam1) through abolishing the inhibitory function of miR-21-5p for Tiam1 expression, thereby promoting the invasion, migration, and proliferation of SW480 colon cancer cells [47]. Moreover, hsa_circ_0020397 inhibited apoptosis and promoted the cell invasion and viability of CRC through enhancing the expression of programmed death-ligand 1 (PD-L1) and telomerase reverse transcriptase (TERT), which are the target genes of miR-138, whereas miR-138 had the opposite effect [51].…”