The N6-methyladenosine modification of circALG1 promotes the metastasis of colorectal cancer mediated by the miR-342-5p/PGF signalling pathway

Abstract

Background Previous studies have shown that the N6-methyladenosine (m6A) modification enhances the binding ability of mRNAs/long noncoding RNAs (lncRNAs) to microRNAs (miRNAs), but the impact of this modification on the competitive endogenous RNA (ceRNA) function of circular RNAs (circRNAs) is unclear. Methods We used a human circRNA microarray to detect the expression profiles of circRNAs in 3 pairs of cancer and paracancerous tissues from patients with colorectal cancer (CRC) and 3 pairs of peripheral blood specimens from patients with CRC and healthy individuals. The circRNAs highly expressed in both peripheral blood and tumour tissues of patients with CRC, including circALG1, were screened. A quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis of an expanded sample size was performed to detect the expression level of circALG1 in peripheral blood and tumour tissues of patients with CRC and determine its correlation with clinicopathological features, and circRNA loop-forming validation and stability assays were then conducted. Transwell assays and a nude mouse cancer metastasis model were used to study the function of circALG1 in CRC and the role of altered m6A modification levels on the regulation of circALG1 function. qRT-PCR, western blot (WB), Transwell, RNA-binding protein immunoprecipitation (RIP), RNA antisense purification (RAP), and dual-luciferase reporter gene assays were performed to analyse the ceRNA mechanism of circALG1 and the effect of the m6A modification of circALG1 on the ceRNA function of this circRNA. Results CircALG1 was highly expressed in both the peripheral blood and tumour tissues of patients with CRC and was closely associated with CRC metastasis. CircALG1 overexpression promoted the migration and invasion of CRC cells, and circALG1 silencing and reduction of the circALG1 m6A modification level inhibited CRC cell migration and invasion. In vivo experiments further confirmed the prometastatic role of circALG1 in CRC. Further mechanistic studies showed that circALG1 upregulated the expression of placental growth factor (PGF) by binding to miR-342-5p and that m6A modification enhanced the binding of circALG1 to miR-342-5p and promoted its ceRNA function. Conclusion M6A modification enhances the binding ability of circALG1 to miR-342-5p to promote the ceRNA function of circALG1, and circALG1 could be a potential therapeutic target in and a prognostic marker for CRC.

m6A-related lncRNAs are potential biomarkers for the prognosis of COAD patients

“…Currently, studies about lncRNA have drawn much attention in various cancer fields. Many lncRNAs can be modified by specific m6A modulators to participate in the tumorigenesis and development (18)(19)(20). Studies have documented that lncRNAs can serve as competitive endogenous RNAs to target m6A modulators, influencing vital cellular functions (21).…”

Hsa_circ_0044301 Regulates Gastric Cancer Cell’s Proliferation, Migration, and Invasion by Modulating the Hsa-miR-188-5p/DAXX Axis and MAPK Pathway

“…The mouse model was constructed using HGC-27 cells, as described previously [ 21 ]. One week after injecting HGC-27 cells at density 1 × 10 7 mL, total 200 μL of cell suspension, BALB/c nude mice were randomly divided into two groups according to tumor volume.…”

Gene signature of m6A RNA regulators in diagnosis, prognosis, treatment, and immune microenvironment for cervical cancer

“…Existing evidence shows that epigenetic modification exists in various molecular biological processes, and it has a significant role in the occurrence and development of cancer 27 – 31 . As the more critical one, m 6 A RNA modification has also been shown to have an important direct relationship with cancers 32 – 36 . In this study, we demonstrated that the expression of m 6 A RNA modification regulators in CC was closely related to its diagnosis and prognosis.…”