MicroRNA-494 promotes cancer progression and targets adenomatous polyposis coli in colorectal cancer

Abstract

BackgroundAberrant activation of the Wnt/β-catenin signaling pathway is frequently observed in colorectal cancer (CRC). β-catenin is the major Wnt signaling pathway effector and inactivation of adenomatous polyposis coli (APC) results in nuclear accumulation of β-catenin. It has been suggested that inactivation of APC plays an important role in activation of the Wnt/β-catenin pathway and in the progression of colorectal tumorigenesis. However, the mechanism through which APC mediates colorectal tumorigenesis is not understood. Increasing evidence suggests that the dysregulation of microRNAs (miRNAs) is involved in colorectal tumorigenesis. Although miR-494 has been reported as being an upregulated miRNA, the interplay between miR-494 and APC-mediated colorectal tumorigenesis progression remains unclear.MethodsThe expression of miR-494 in tissues from patients diagnosed with CRC was analyzed using a microarray and real-time PCR. The effects of miR-494 on cell proliferation and tumorigenesis in CRC cells were analyzed by flow cytometry, colony formation assays, BrdU incorporation assays, and CCK8 assays. The correlation between miR-494 expression and APC expression, as well as the mechanisms by which miR-494 regulates APC in CRC were also addressed.ResultsmiR-494 was significantly upregulated in CRC tissues, and this increase was negatively associated with APC expression. APC was confirmed to be a direct target of miR-494 in CRC. Furthermore, overexpression of miR-494 induced Wnt/β-catenin signaling by targeting APC, thus promoting CRC cell growth.ConclusionsThis study provides novel insights into the role of miR-494 in controlling CRC cell proliferation and tumorigenesis, and identifies miR-494 as a potential prognostic marker and therapeutic target.

MicroRNA‑494 promotes the proliferation and migration of human glioma cancer cells through the protein kinase�B/mechanistic target of rapamycin pathway by phosphatase and tensin homolog expression

“…Taken together, the results of the present study suggested that miR494 acts as an oncogene in glioma. Zhang et al (16) reported that microRNA-494 promotes colorectal, epithelial ovarian (17) and pancreatic cancer (18). These results are in line with those of the present study and demonstrated that miR-494 participates in the development and progression of glioma.…”

“…Meanwhile, PI3K and Akt may be effective targets for the clinical treatment of glioma cancer (15). Zhang et al (16) reported that miRNA-494 promotes colorectal (16), epithelial ovarian (17) and pancreatic cancer (18). The aim of the present study was to analyze the possible association between microRNA-494 and cell proliferation in glioma.…”

MNX1 promotes cell proliferation and activates Wnt/β‐catenin signaling in colorectal cancer

“…Subsequently, the β‐catenin will be release from the complex, which induces the accumulation of β‐catenin in cytoplasm. Then, β‐catenin translocates from cytoplasm to nucleolus, where β‐catenin is able to form a complex with the T‐cell factor/lymphoid enhancer factor binding factor (TCF/LEF) transcription factors and results in the transcription of Wnt target genes, such as c‐Myc and CCND1 , which enhances cell proliferation and tumorigenesis (Morin et al, ; Liu et al, ; Zhang et al, ). However, the detailed mechanisms by which the Wnt/β‐catenin is activated in CRC are not fully known.…”

A miR-494 dependent feedback loop regulates ER stress

“…While miRs have a recognized role in liver disease (50), our studies are the first to show the ER stress reducing activity of miR-494 in the context of liver disease (NASH). miR-494 is known to be oncogenic and drives tumor progression and drug resistance in specific cancer types including colorectal cancer (51) and hepatocellular carcinoma (52,53). Furthermore, miR-494 has been shown to attenuate ischemia reperfusion injury in the liver by regulating the PI3K/Akt signaling pathway (54).…”