Hsa-miR-3658 down-regulates OCT4 gene expression followed by suppressing SW480 cell proliferation and migration

Abstract

The pluripotency factor, OCT4 gene is a stemness marker that is involved in the tumorigenicity of different cancer types and knowing about molecular mechanisms of its regulation is crucially important. To date, a few microRNAs (miRNAs) are known to be regulators of OCT4 gene expression. Looking for the novel miRNAs which are capable of regulating OCT4 gene expression, our bioinformatics analysis introduced hsa-miR-3658 (miR-3658) as a bona fide candidate. Then, RT-qPCR results indicated that miR-3658 expression is decreased in colorectal cancer (CRC) tumor tissues, compared with normal pairs. Furthermore, RT-qPCR and western blot analysis showed that the OCT4 gene has been down-regulated following the miR-3658 overexpression. Consistently, dual-luciferase assay supported the direct interaction of miR-3658 with the 3′-UTR sequence of OCT4 gene. Unlike in HCT116 cells, overexpression of miR-3658 in SW480 cells brought about growth inhibition, cell cycle arrest and reduced cell migration, detected by flow cytometry, and scratch test assay. Overall, these findings demonstrated that miR-3658 as a tumor suppressor miRNA exerts its effect against OCT4 gene expression, and it has the potential of being used as a prognostic marker and therapeutic target against colorectal cancer.

Glaucocalyxin A Inhibits the Malignancies of Gastric Cancer Cells by Downregulating MDM2 and RNF6 via MiR-3658 and the SMG1-UPF mRNA Decay Pathway

“…MiRNAs target downstream genes by interacting with the specific binding site in the three prime untranslated regions (3'-UTR) in mRNA. MiRNAs have been documented to be involved in GC initiation and progression, and the pattern of deregulated miRNAs represents the features related to diagnosis, prognosis, and therapeutic resistance in GC (16)(17)(18)(19). Recent data have revealed that miR-3658 acts as tumor suppressor miRNA in colorectal cancer by targeting octamer-binding transcription factor 4 (Oct4) (17).…”

“…MiRNAs have been documented to be involved in GC initiation and progression, and the pattern of deregulated miRNAs represents the features related to diagnosis, prognosis, and therapeutic resistance in GC (16)(17)(18)(19). Recent data have revealed that miR-3658 acts as tumor suppressor miRNA in colorectal cancer by targeting octamer-binding transcription factor 4 (Oct4) (17). In addition to deregulated RNA silencing by miRNAs that occurred at the posttranscriptional level in cancer cells, the impairment of the nonsense-mediated mRNA decay (NMD) mechanism plays a critical role in driving the onset and progression of cancer via posttranscriptional regulation (20).…”