Abstract
To investigate the role of microRNA-497-5p (miR-497-5p) in the tumorigenesis of colorectal cancer (CRC), the present study applied qRT-PCR to detect the expression level of miR-497-5p in both clinical samples and CRC cell lines. Furthermore, to specifically evaluate the carcinogenic role of miR-497-5p in CRC, the expression of miR-497-5p was monitored by transfecting with the mimics or inhibitors of miR-497-5p. Transwell assay as well as CCK-8 assay were used to determine the functions of miR-497-5p on cell invasion, migration and proliferation, respectively. miR-497-5p expression was remarkably down-regulated in clinical samples with cancer development as well as in CRC cell lines. Additionally, low miR-497-5p expression was remarkably correlated with higher TNM stage and lymph node metastasis of CRC patients. Up-regulation of miR-497-5p significantly inhibited proliferation, migration, and invasion of LOVO CRC cell line. Conversely, antagonizing miR-497-5p significantly promoted cell proliferation, migration and invasion. Mechanistic analysis revealed that miR-497-5p directly bound to its downstream target, protein tyrosine phosphatase non-receptor type 3 (PTPN3), whose aberrant expression partially reversed inhibition of cell proliferation and migration. Taken together, the present study elucidated the inhibitory role of miR-497-5p in CRC via targeting PTPN3, which potentiated miR-497-5p as a potential therapeutic target for combating CRC.
Highlights
Colorectal cancer (CRC) emerges as one of the most common gastrointestinal malignancies and ranks second in cancer deaths worldwide [1]
SW480, HT29, LOVO, SW620 human CRC cell lines were acquired from American Type Culture Collection (ATCC; U.S.A.) and they were maintained in RPMI 1640 (PAA, Gemany) supplemented with 10% fetal bovine serum (Hyclone, Logan, UT) and 100 U/ml penicillin (Life Technologies Corporation)
MiR-497-5p expression in CRC was negatively correlated with pathological tumor-nude-metastasis (pTNM) stage (P=0.004, Figure 1E)
Summary
Colorectal cancer (CRC) emerges as one of the most common gastrointestinal malignancies and ranks second in cancer deaths worldwide [1]. Despite the advancement of diagnostic technologies and treatment management in the past decades, long-term survival rate in patients with CRC remains extremely low due to inadequate diagnosis and treatment in early stages of carcinoma [2–4]. The molecular mechanism regarding hepatic metastases of colon and rectal carcinoma remains largely unknown. MicroRNAs (miRNAs) have approximately 21 nucleotides in length. They are among one category of small noncoding RNAs and post-transcriptionally regulate genes expression via translational suppression as well as destabilization of target mRNAs [5,6]. Aberrant miRNA expression was found in various tumors, including prostate cancer, breast cancer, hepatocellular carcinoma, lung cancer as well as colon cancer, indicating the close relevance between miRNAs
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