miR-204-5p expression in colorectal cancer: an autophagy-associated gene

Abstract

MicroRNAs (miRNAs) are important factors during tumorigenesis by affecting posttranscriptional gene expression. miRNA 204 (miR-204) is a miRNA frequently investigated in different types of cancers. According to literature, autophagy has dual roles in cancer, acting as both a tumor suppressor and cell survival agent. Also, the current data suggests that autophagy is activated in human colorectal cancer cells and enhances the aggressiveness of human colorectal cancer cells. So, our aim is to investigate potential effect of miR-204-5p on colorectal cancer by associating its expression with autophagy-related targets of miR-204-5p. This is the first miRNA study conducted on patients with colorectal cancer and healthy subjects and also to search the relation of miR-204-5p with clinicopathological factors and survival. Sixty-six patients with colorectal cancer and healthy subjects without any known chronic disease were enrolled into our study. Total miRNA was isolated from paraffin-embedded tissues of all patients' cancerous and normal tissues, and healthy subjects. cDNAs were obtained from this miRNAs by reverse transcriptase method, and miR-204-5p relative expression levels were detected by qRT-PCR method. Patients were divided into two groups according to median relative expression levels of miR-204-5p, as low- and high-expression group. Relation of miR-204-5p with clinicopathological factors and overall survival was also investigated. Medians of miR-204-5p relative expression levels in cancerous and normal tissues of patients were found as 0.00235 and 0.00376, respectively. The difference between two groups was not statistically significant (p = 0.11). Nonetheless, median of miR-204-5p relative expression levels in healthy subjects were found as 0.00135, and the difference between patient with cancer and healthy subjects and between normal tissues of patients and healthy subjects were statistically significant (p = 0.021 and p = 0.0005, respectively). There were 32 patients (48.5 %) showing high expression and 34 patients (51.5 %) showing low expression according to miR-204-5p relative expression levels. There were no statistically significant relation between clinicopathologic features and miR-204-5p relative expression levels. We also investigated the relation between miR-204-5p relative expression levels and overall survival, and no statistically significant relation was found between them (p = 0.462). The absence of any significant difference between tumor and non-tumor samples, low sample size, and performance at just one center are the limitations of our study. In opposition to literature, miR-204-5p is overexpressed in colorectal cancer patients as compared with healthy subjects and this situation is not associated with clinicopathological factors and overall survival. This may be explained by the fact that miR-204-5p increases in colorectal cancer cases in order to inhibit increased activity of LC3B-II in autophagy and Bcl2 against apoptosis posttranscriptionally and to take role as tumor suppressor.

Regulation of multidrug resistance by microRNAs in anti-cancer therapy

“…Therefore, these two pathways might have cross-talk, and be regulated by the same miRNA. For example, miR-204 shows both an anti-apoptosis effect and autophagy inhibitory effect155, 156. Up or down regulation of miR-204 may change the transition of apoptosis and autophagy; subsequently, influence chemosensitivity.…”

miR‐204‐5p targeting SIRT1 regulates hepatocellular carcinoma progression

“…miR‐204‐5p can promote or suppress cancer progression; however, its role in HCC is not clear. In the present study, the expression and role of miR‐204‐5p in HCC will be studied.…”

miR-10a and miR-204 as a Potential Prognostic Indicator in Low-Grade Gliomas

“…In addition, Yin et al26 reported that miR-204-5p can inhibit cell survival and accelerate the impact of CT in colorectal cancer. However, these results were contradicted by Sümbül et al,27 who reported significantly higher levels of miR-204-5p in colorectal cancer than in a healthy group. In the latter study, it was suggested that the increased expression of miR-204-5p in colorectal cancers acted to overcome cellular autophagy by inhibiting the expression of LC3B-II and Bcl-2 .…”