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.

Associations of sirtuins with clinicopathological variables and prognosis in human ovarian cancer

“…In the present study, SIRT5 overexpression was associated with a favorable prognosis in OC, and elevated SIRT5 levels in patients with clinical stage III+IV and TP53 mutations were associated with improved OS, implying that SIRT5 is a potential biomarker of OC. Previous studies referring to SIRT6 have investigated its role as a tumor suppressor, and its decreased expression is associated with poor OS in patients with pancreatic cancer (44), hepatic carcinoma (45) and colon cancer (46). The present study demonstrated that SIRT6 overexpression was associated with good prognosis in OC.…”

The study of mechanism of miR-34c-5p targeting FLOT2 to regulate proliferation, migration and invasion of osteosarcoma cells

“…While miR-99a [20]and miR-21 [21] are highly expressed in osteosarcoma tissues and cells, down-regulation of their expression inhibits osteosarcoma cell proliferation, invasion and metastasis, and promotes apoptosis. Interestingly, miR-34c-5p functions as a carcinogen in various cancers, such as colon cancer [22] and bladder cancer [23]. However, increasing evidence indicates that miR-34c-5p acts as a tumor suppressor in various tumors, such as acute myeloid leukemia [24].…”

An in silico approach to identify and prioritize miRNAs target sites polymorphisms in colorectal cancer and obesity

“…In this case, the miR-30 family, miR-504, miR-34c, miR-488, miR-15b, miR-195, miR-497, miR-15a, miR-503, miR-141, miR-182, miR-96, and miR-136 were also related to invasion, proliferation, metastasis and tumor growth, or survival of several cancers including CRC. [46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65] However, there are few studies on the role of included prioritized miRNAs for interactions with obesity. For obesity there are some studies on mice, for instance, miR-16-5p decrease with high weight and a mutation in miR-16 gene lead to increasing in body weight.…”