Circ3823 contributes to growth, metastasis and angiogenesis of colorectal cancer: involvement of miR-30c-5p/TCF7 axis

Abstract

Background Colorectal cancer (CRC) is one of the most common malignant tumours. The recurrence and metastasis of CRC seriously affect the survival rate of patients. Angiogenesis is an extremely important cause of tumour growth and metastasis. Circular RNAs (circRNAs) have been emerged as vital regulators for tumour progression. However, the regulatory role, clinical significance and underlying mechanisms still remain largely unknown. Methods High-throughput sequencing was used to analyse differential circRNAs expression in tumour and non-tumour tissues of CRC. In situ hybridization (ISH) and qRT-PCR were used to determine the level of circ3823 in CRC tissues and serum samples. Then, functional experiments in vitro and in vivo were performed to investigate the effects of circ3823 on tumour growth, metastasis and angiogenesis in CRC. Sanger sequencing, RNase R and Actinomycin D assay were used to verify the ring structure of circ3823. Mechanistically, dual luciferase reporter assay, fluorescent in situ hybridization (FISH), RNA immunoprecipitation (RIP) and RNA pull-down experiments were performed to confirm the underlying mechanisms of circ3823. Results Circ3823 was evidently highly expressed in CRC and high circ3823 expression predicted a worse prognosis of CRC patients. Receiver operating characteristic curves (ROCs) indicated that the expression of circ3823 in serum showed high sensitivity and specificity for detecting CRC which means circ3823 have the potential to be used as diagnostic biomarkers. Functional experiments in vitro and in vivo indicated that circ3823 promote CRC cell proliferation, metastasis and angiogenesis. Mechanism analysis showed that circ3823 act as a competing endogenous RNA of miR-30c-5p to relieve the repressive effect of miR-30c-5p on its target TCF7 which upregulates MYC and CCND1, and finally facilitates CRC progression. In addition, we found that N6-methyladenosine (m6A) modification exists on circ3823. And the m6A modification is involved in regulating the degradation of circ3823. Conclusions Our findings suggest that circ3823 promotes CRC growth, metastasis and angiogenesis through circ3823/miR-30c-5p/TCF7 axis and it may serve as a new diagnostic marker or target for treatment of CRC patients. In addition, m6A modification is involved in regulating the degradation of circ3823.

CircMET promotes tumor proliferation by enhancing CDKN2A mRNA decay and upregulating SMAD3

“…Increasing studies revealed the important functions of ceRNA network in tumor proliferation, antiapoptosis, metastasis and other tumor development processes. For example, circ3823 contributes to growth, metastasis and angiogenesis of colorectal cancer by absorbing miR-30c-5p and mediating TCF7 [ 48 ]. In addition to this, the resistant tumors showed significant expression changes of circRNAs, CircMEMO1 modulates the promoter methylation by acting as a sponge for miR-106b-5p to regulate sorafenib treatment sensitivity of hepatocellular carcinoma [ 49 ].…”

The crosstalk between reactive oxygen species and noncoding RNAs: from cancer code to drug role

“…MiR-30c-5p was reported to be an important OS regulator by multiple studies [ 86 – 88 ]. In colorectal cancer, circ3823 functioned as a ceRNA of miR-30c-5p, alleviating the repressive effect of miR-30c-5p on TCF7 which upregulated MYC and CCND1 and eventually led to cancer initiation and metastasis [ 89 ]. Hu et al identified an oncogenic circASAP1 through circRNA sequencing in patients with HCC, which was proved to be associated with cancer initiation and metastasis via miR-326/miR-532-5p-MAPK1/CSF-1 signaling, respectively [ 90 ].…”

Salivary miR-30c-5p as Potential Biomarker for Detection of Oral Squamous Cell Carcinoma

“…However, the possible role of miR-30c-5p as a biomarker for early diagnosis or development of recurrence needs further investigation. miR-30c-5p studied here has been shown to be involved in other cancers such as colorectal cancer [32,33], non-small cell lung cancer [34,35], gastric cancer [36], pancreatic ductal adenocarcinoma [37], renal cell carcinoma [38,39], hepatocellular carcinoma [40][41][42][43], breast cancer [44][45][46][47][48], laryngeal cancer [49], and other malignancies. For example, in gastric cancer, miR-30c-5p suppresses migration, invasion, and epithelial to mesenchymal transition via targeting MTA1 [36].…”