Circ_0006174 Accelerates Colorectal Cancer Progression Through Regulating miR-138-5p/MACC1 Axis

Abstract

Background Circular RNAs (circRNAs) were reported to be involved in the progression of a variety of cancers, including colorectal cancer (CRC). However, the precise functions and mechanism of circRNAs in CRC have not been elucidated. This study aimed to investigate the effect and mechanism underlying circ_0006174 in CRC. Methods The expression of circ_0006174, microRNA (miR-138-5p) and metastasis associated in colon cancer 1 (MACC1) mRNA was detected by quantitative real-time polymerase chain reaction (RT-qPCR) assay. Western blot was employed to measure MACC1 protein expression. The effects of circ_0006174 knockdown, MACC1 overexpression or miR-138-5p inhibition on cell proliferation, migration, invasion, and apoptosis were assessed by cell counting kit 8 (CCK-8) assay, clone formation assay, transwell assay and flow cytometry assay, respectively. The interaction between miR-138-5p and circ_0006174 or MACC1 was confirmed by RNA pull down assay or dual-luciferase reporter assay. Xenograft tumor model in nude mice was used to verify the function of circ_0006174 in vivo. Results Circ_0006174 and MACC1 expression was highly expressed, while miR-138-5p expression was downregulated in CRC cells and tissues. Meanwhile, circ_0006174 functioned as a sponge of miR-138-5p to upregulate MACC1 expression. Furthermore, circ_0006174 knock down-mediated suppression on cell proliferation, migration and invasion, and promotion on cell apoptosis could be alleviated by MACC1 overexpression or miR-138-5p inhibition in CRC cells. Besides, circ_0006174 knockdown also inhibited CRC procession in vivo. Conclusion Circ_0006174 advanced CRC progression via sponging miR-138-5p to upregulate MACC1 expression, which may provide a promising molecular target for CRC treatment.

Circ_0006174 promotes colorectal cancer progression by sponging microRNA-142-3p and regulating X-linked inhibitor of apoptosis expression

“…Notably, a recent study reports that circ_0006174 is up-regulated in CRC tissues, and overexpression of circ_0006174 promotes CRC cell proliferation, migration and invasion in vitro, and enhances xenograft tumour growth in BALB/c mice by up-regulating MACC1. 7 This report is similar to the findings of our study.…”

“…6 Moreover, it is reported that circ_0006174 promotes CRC progression by regulating the miR-138-5p/ MACC1 axis. 7 However, the molecular mechanism by which circ_0006174 exerts its effects has not been fully elucidated.…”

Circ_0006174 promotes the malignancy of colorectal cancer cell via the miR‑1205/CCBE1/Wnt pathway

“…circ_0006174 is a circRNA which is transcribed from chromosome chr9:110064315-110068928+. A previous study reports that circ_0006174 is highly expressed in CRC tissues and cells that and circ_0006174 can promotes CRC progression via sponging miR-138-5p and upregulating MACC1 ( 8 ). Another study reports that the exosomal circ_0006174 promotes doxorubicin resistance of CRC cells ( 9 ).…”

“…In order to explore the novel circRNAs which participate in CRC progression, the present study analyzed a microarray dataset (GSE138589) in the Gene Expression Omnibus (GEO) database and identified a circRNA, circ_0006174, which is upregulated in CRC tissues. Some previous studies have reported that circ_0006174 promotes CRC progression and contributes to the chemoresistance of doxorubicin ( 8 , 9 ). Nevertheless, its role and mechanism in CRC remains to be elucidated.…”

Oncogenic Functions and Clinical Significance of Circular RNAs in Colorectal Cancer

“…Hsa_circ_0006174 acts as miR-138-5p sponge and the followed upregulator of MACC1 (Metastasis-associated in colon cancer protein 1) [ 155 ]. MACC1 is a transcription factor which, via HGF/cMET axis, is involved in EMT in CRC [ 156 ].…”