MicroRNA-466 (miR-466) functions as a tumor suppressor and prognostic factor in colorectal cancer (CRC)

Abstract

MicroRNAs (miRNAs) have an important role in the regulation of tumor development and metastasis. In this study, we investigated the clinical and prognostic value as well as biological function of miR-466 in colorectal cancer (CRC). Tumor and adjacent healthy tissues were obtained from 100 patients diagnosed with CRC. miR-466 expression was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). mRNA and protein levels of cyclin D1, apoptosis regulator BAX (BAX), and matrix metalloproteinase-2 (MMP-2) were analyzed by qRT-PCR and Western blot, respectively, in SW-620 CRC cells transfected with miR-466 mimics or negative control miRNA. Effects of miR-466 on SW-620 cell proliferation, cell cycle and apoptosis, and invasion were investigated using CCK-8 assay, flow cytometry and Transwell assay, respectively. miR-466 expression was significantly downregulated in tumor tissues compared to matched adjacent non-tumor tissues. Low expression of miR-466 was significantly correlated with the tumor size, Tumor Node Metastasis stage, lymph node metastasis, and distant metastasis. The overall survival of CRC patients with low miR-466 expression was significantly shorter compared to high-miR-466 expression group (log-rank test: p = 0.0103). Multivariate analysis revealed that low miR-466 expression was associated with poor prognosis in CRC patients. The ectopic expression of miR-466 suppressed cell proliferation and migration/invasion, as well as induced G0/G1 arrest and apoptosis in SW-620 cells. Moreover, the ectopic expression of miR-466 decreased the expression of cyclin D1 and MMP-2, but increased BAX expression in SW-620 cells. In conclusion, our findings demonstrated that miR-466 functions as a suppressor miRNA in CRC and may be used as a prognostic factor in these patients.

Overexpression of microRNA‐98 inhibits cell proliferation and promotes cell apoptosis via claudin‐1 in human colorectal carcinoma

“…3 CRC has been reported to be prevalent in the elderly with an average age of about 71 years old; however, the average age of CRC has been falling in recent years; so the incidence of the disease in people under 50 years are afflicted. 3 CRC has been reported to be prevalent in the elderly with an average age of about 71 years old; however, the average age of CRC has been falling in recent years; so the incidence of the disease in people under 50 years are afflicted.…”

Tissue micro-RNAs associated with colorectal cancer prognosis: a systematic review

“…Twenty-four studies demonstrated the downregulation of twenty-five miRs associated with advanced TNM stage: miR-302c 67 , miR-466 68 , miR-340 69 , miR-196b-5p 70 , miR-944 71 , miR-30d 72 , miR-22 50 , miR-296 73 , miR-384 74 , miR-199b 48 , miR-128 75 , miR-33b 76 , miR-155-5p 77 , miR-154 78 , miR-149 79 , miR-194 80 , miR-133b 37 , miR-15a 34 , miR-100 81 , miR-133a 41 , miR-335 82 , miR-378a-3p 58 , miR-378a-5p 58 , miR-218 83 and miR-16 34 . Two studies demonstrated the upregulation of miR-182 43, 44 associated with advanced TNM stage and others 22 studies pointed 23 different upregulated miRs associated with advanced TNM stage.…”

Genome‐wide identification of a novel miRNA‐based signature to predict recurrence in patients with gastric cancer

“…These results are consistent with previous research showing that miR‐181b was involved in transforming growth factor beta‐induced epithelial‐to‐mesenchymal transition and GC metastasis (Zhou et al ., ). Considering protective factors, we noted that miR‐145 could inhibit the malignant phenotypes and suppress metastasis of GC via different molecular mechanisms (Gao et al ., ; Lei et al ., ; Tong et al ., ; Xing et al ., ; Xue et al ., ; Zheng et al ., ). In another study, miR‐7‐3 was confirmed to be an independent prognostic indicator for stomach adenocarcinoma (Huo, ).…”

“…In another study, miR‐7‐3 was confirmed to be an independent prognostic indicator for stomach adenocarcinoma (Huo, ). Two miRNAs, miR‐466 and miR‐3144, have been indicated as tumor suppressors in other types of cancers (Colden et al ., ; Lin et al ., ; Tong et al ., ), although there are no data available regarding their roles in GC. Other miRNAs, miR‐365a, miR‐3923, miR‐549a, miR‐378i and miR‐4793, are also reported for the first time in GC in the present study.…”

“…Time-dependent ROC curves to compare the prognostic accuracy of the 11-miRNA classifier with tumor stage in the training cohort (A, B) and validation cohort (C). Tong et al, 2018), although there are no data available regarding their roles in GC. Other miR-NAs, miR-365a, miR-3923, miR-549a, miR-378i and miR-4793, are also reported for the first time in GC in the present study.…”