Abstract
Dysregulation of microRNAs (miRNAs) and their targeted downstream genes is involved in the carcinogenesis and progression of colorectal cancer (CRC). miR-519b-3p has been reported to play an important role in several cancers. However, its function in CRC is unclear. In this study, we detected the expression of miR-519b-3p in CRC tissues and cell lines, and determined the potential role of miR-519b-3p in cell proliferation and invasion in CRC. Also, the downstream gene of miR-519b-3p was determined. Our results showed that miR-519b-3p was notably reduced in CRC specimens and cell lines. Overexpression of miR-519b-3p inhibited the proliferation and invasion of RKO and DLD-1 cells, whereas knockdown of miR-519b-3p had the contrary effect. The ubiquitous mitochondrial creatine kinase (uMtCK) was identified as a direct target of miR-519b-3p in CRC using luciferase assay. Additionally, miR-519b-3p expression was negatively correlated with uMtCK expression in CRC specimens. Notably, the miR-519b-3p suppressed the uMtCK/Wnt signaling pathway in CRC cells, thereby suppressing CRC cell proliferation and invasion. The inhibition of uMtCK by miR-519b-3p may provide a promising option for the treatment of CRC.
Highlights
Colorectal cancer (CRC) is one of the most common cancer types globally, with 1.2 million new diagnosed cases as well as 600,000 fatalities annually (Siegel et al, 2015; Moriarity et al, 2016)
Cell Counting Kit-8 (CCK-8) assay showed that miR-519b-3p overexpression suppressed colorectal cancer (CRC) cell proliferation (Figure 2B)
Our data showed that miR-519b-3p was dramatically down-regulated in CRC cell lines and tissues, and overexpression of miR-519b-3p suppressed CRC cell proliferation and invasion
Summary
Colorectal cancer (CRC) is one of the most common cancer types globally, with 1.2 million new diagnosed cases as well as 600,000 fatalities annually (Siegel et al, 2015; Moriarity et al, 2016). MicroRNAs (miRNAs) are a class of small, single-strand, non-coding RNA with 18–25 nucleotides in length (Asangani et al, 2008). They bind to the three prime untranslated region (3′-UTR) segments of messenger RNAs, inhibiting the expression of target genes in human cancers, including CRC, Role of miR-519b-3p in Colorectal Cancer in which they act as tumor suppressor genes or oncogenes (Liao et al, 2013). Increasing number of studies show that miRNA dysregulation occurs in both early and late stages of CRC. Dysregulation of these miRNAs could induce cell proliferation, apoptosis, angiogenesis, and metastases in CRC (Chen et al, 2009; Tsang and Kwok, 2009).
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