Downregulation of SIRT6 by miR-34c-5p is associated with poor prognosis and promotes colon cancer proliferation through inhibiting apoptosis via the JAK2/STAT3 signaling pathway.

Abstract

Sirtuin 6 (SIRT6) is a member of the nicotinamide adenine dinucleotide positivity-dependent class III deacetylase sirtuin family. The present study aimed to explore the expression and function of SIRT6 in colon cancer. Furthermore, the partial mechanism underlying the dysregulation of SIRT6 was investigated. The results of immunohistochemistry demonstrated that SIRT6 was markedly downregulated in colon cancer tissues, and patients with high SIRT6 expression had a better prognosis than those who did not. The proliferation and apoptotic assays demonstrated that SIRT6 was able to suppress colon cancer cell proliferation and induce apoptosis via the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. MicroRNAs (miRNAs/miRs) are important non-coding RNAs, which have a critical role in the negative regulation of their target genes. Through bioinformatics analysis and further experiments, the results demonstrated that miR-34c-5p was not only dysregulated in colon cancer tissues but may also regulate SIRT6 expression via interaction with the 3′-untranslated region of SIRT6 mRNA. The proliferation and apoptotic assays indicated that miR-34c-5p could directly promote cell growth and inhibit apoptosis via activation of the JAK2/STAT3 signaling pathway, which was similar to silencing SIRT6. In conclusion, the results of the present study demonstrated that miR-34c-5p promoted colon cancer cell proliferation by targeting SIRT6 via activation of the JAK2/STAT3 signaling pathway. It may be hypothesized that SIRT6 is a potential biomarker for colon cancer prognosis, and the miR-34c-5p/SIRT6/JAK2/STAT3 axis may provide novel insights into colon cancer treatment.