Published online Feb 15, 2023. doi: 10.4251/wjgo.v15.i2.318
Peer-review started: September 22, 2022
First decision: October 21, 2022
Revised: November 4, 2022
Accepted: December 30, 2022
Article in press: December 30, 2022
Published online: February 15, 2023
Processing time: 145 Days and 22.2 Hours
microRNA-627-5p (miR-627-5p) dysregulation has been observed in several cancer types, such as hepatocellular carcinoma, oral squamous cell carcinoma, glioblastoma multiforme, and gastric cancer. The biological function of miR-627-5p in colorectal cancer (CRC) growth and metastasis is yet unclear.
To investigate the effects of miR-627-5p on the malignant biological properties of colorectal malignant tumour cells by targeting Wnt2.
The levels of miR-627-5p in colorectal tumour tissues were assessed in Gene Expression Omnibus datasets. In order to identify Wnt2 transcript expression in CRC tissues, quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used. Luciferase reporter tests were used to explore whether miR-627-5p might potentially target Wnt2. Wnt2 transcript and protein levels were detected in CRC cells with high miR-627-5p expression. To learn more about how miR-627-5p affects CRC development, migration, apoptosis, and invasion, functional experiments were conducted. Cotransfection with the overexpression vector of Wnt2 and miR-627-5p mimics was utilized to verify whether overexpression of Wnt2 could cancel the impact of miR-627-5p in CRC. Western blot and qRT-PCR were conducted to investigate the effects of miR-627-5p on the Wnt/β-catenin signalling pathway.
miR-627-5p was notably decreased in colorectal tumour tissues, while the gene level of Wnt2 was notably upregulated. A dual luciferase reporter assay revealed that miR-627-5p specifically targets the 3’-untranslated regions of Wnt2 and miR-627-5p upregulation markedly reduced the protein and gene expression of Wnt2 in CRC cells. In vitro gain-of-function assays displayed that miR-627-5p overexpression decreased CRC cells’ capabilities to invade, move, and remain viable while increasing apoptosis. Wnt2 overexpression could reverse the suppressive functions of miR-627-5p. Moreover, upregulation of miR-627-5p suppressed the transcript and protein levels of the downstream target factors in the canonical Wnt/β-catenin signalling, such as c-myc, CD44, β-catenin, and cyclinD1.
miR-627-5p acts as a critical inhibitory factor in CRC, possibly by directly targeting Wnt2 and negatively modulating the Wnt/β-catenin signalling, revealing that miR-627-5p could be a possible treatment target for CRC.
Core Tip: It has been well established that miRNAs play vital roles in modulating cancer-related pathways, thereby regulating colorectal cancer (CRC) growth and metastasis. The study comprehensively explored the function of microRNA-627-5p (miR-627-5p), a rarely reported miRNA in CRC. miR-627-5p mimics restrained CRC cells invasion, migration, proliferation, and promoted cell apoptosis, indicated its suppressive effects on CRC development. A dual luciferase reporter test showed miR-627-5p directly binds with the 3’-untranslated region of Wnt2. Furthermore, miR-627-5p prevented the aggressive behaviours of cancer cells via inhibiting the activation of the canonical Wnt signalling. Strategies targeting the miR-627-5p/Wnt2/β-catenin signalling might be a new treatment option for CRC.