Circular RNA circFAT1(e2) Promotes Colorectal Cancer Tumorigenesis via the miR-30e-5p/ITGA6 Axis.

Fei Pan,Mei Liu,Dongqing Zhang,Na Li,Tao Huang

doi:10.1155/2021/9980459

Abstract

circRNAs (circular RNAs) are a family of noncoding RNAs and have diverse physiological and pathological functions. However, the functions and mechanisms of circRNAs in the development and progression of colorectal cancer (CRC) remain largely unknown. Here, we aimed to explore the functions and roles of circFAT1(e2) in CRC. qRT-PCR revealed that circFAT1(e2) in CRC tumor tissues was upregulated compared with that in adjacent normal tissues and was also upregulated in CRC cell lines. Small interfering RNAs (siRNAs) against circFAT1(e2) were used to decrease the expression of circFAT1(e2) in HCT116 and RKO cells in vitro. The roles of circFAT1(e2) in CRC cell metastasis and proliferation were then determined by transwell and CCK-8 assays. The results showed that circFAT1(e2) silencing markedly suppressed CRC growth. Moreover, we identified circFAT1(e2) as a promoter of CRC metastasis. Knockdown of circFAT1(e2) evidently reduced HCT116 and RKO cell migration and invasion. Furthermore, the regulatory relationship between circFAT1(e2) and its target miRNAs was verified by a luciferase reporter assay. We demonstrated that circFAT1(e2) could sponge miR-30e-5p, which regulated the expression level of integrin α6 (ITGA6), the downstream target gene of miR-30e-5p. Rescue assays demonstrated that knockdown of miR-30e-5p enhanced CRC proliferation and migration via ITGA6. Taken together, our results reveal the novel oncogenic roles of circFAT1(e2) in CRC through the miR-30e-5p/ITGA6 axis.

Highlights

CircRNA is a special type of noncoding RNA with a closedloop structure in eukaryotic cells produced by the reverse splicing process
The identification of novel biomarkers is important for the early diagnosis and monitoring of colorectal cancer (CRC)
The high expression of serum miR-92a is related to the poor prognosis of patients with CRC [22]. miR-135b can be used as a molecular marker for early screening for CRC [1]. miR106a is more stable than miR-135b, which can increase the sensitivity of faecal detection [23]

Summary

Introduction

CircRNA is a special type of noncoding RNA with a closedloop structure in eukaryotic cells produced by the reverse splicing process. Little is known about circRNAs in human diseases due to the lack of powerful technical methods [3]. With the creation and improvements of next-generation sequencing technology and biological methods, emerging studies have demonstrated that circRNAs play important roles in human cancers [4,5,6]. Overexpression of circRNA_102171 was found to promote cancer progression by activating the Wnt/β-catenin pathway in a CTNNBIP1-dependent manner [7]. CircRNA_0000285 can promote the proliferation and metastasis of cervical cancer by upregulating FUS and can be used as a potential target for cervical cancer treatment [9]. Exploring the functions of circRNAs in cancers could provide novel biomarkers for cancer treatment [11, 12]

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