SIRT6 Promotes the Progression of Prostate Cancer via Regulating the Wnt/β-Catenin Signaling Pathway

Abstract

Sirtuin 6 (SIRT6), a DNA repair-related gene, has undergone an extremely thorough study for its involvement in the development of many different cancers. The objective of our study was to explore the function and mechanism of SIRT6-induced regulation of prostate cancer (PCa). RT-PCR was performed to validate the levels of SIRT6 in PCa cell lines. Cell proliferation, migration, and invasion of cells with SIRT6 knockdown were assessed using CCK-8 assay, colony formation assay, wound-healing assay, and transwell assay. Western blot was applied to assess the related proteins. We found that SIRT6 expression was distinctly upregulated in PCa specimens and cells. Loss-of-functional assays revealed that SIRT6 silence suppressed the proliferation and metastasis of PCa cells. Mechanistic studies revealed that SIRT6 silence inhibited Wnt/β‐catenin signaling and EMT progress. Overall, the study confirmed the upregulation of SIRT6 in patients with PCa and its association with the progression. SIRT6 promoted PCa progression by regulating Wnt/β‐catenin signaling, providing a promising biomarker and treatment approach for preventing PCa.

Exploring the therapeutic potential of Sirt6-enriched adipose stem cell-derived exosomes in myocardial ischemia–reperfusion injury: unfolding new epigenetic frontiers

“…In other conditions, Sirt6 functions according different disease contexts. Several studies have confirmed Sirt6 as both an oncogenic factor [ 40 ] and a tumor suppressor in some cancers [ 41 ]. Each member of Sirtuin family has a series of target proteins, and the functions of target proteins may be decided by the pathological conditions, intensity of stimuli, time point of intervention, and the effector organ, which may result in the inconsistency of the final outcome of regulation of Sirt6.…”

The Role of NAD+, SIRTs Interactions in Stimulating and Counteracting Carcinogenesis

“…Furthermore, SIRT6 inhibits the IGF/AKT pathway, which is responsible for suppressing autophagy [193], while activating the PI3K/AKT/mTOR pathway, which promotes cancer progression [189]. Finally, SIRT6 regulates the transmission of Wnt/β-catenin signals, which contribute to the progression of cancer [194] (Tables 4 and 5).…”

The Mechanistic Roles of Sirtuins in Breast and Prostate Cancer

“…Unlike in other types of cancer, including breast cancer, SIRT6 is overexpressed in prostate tumor tissues and cells (PC3, DU145, 22RV1, and LNCaP), with high SIRT6 expression correlating with poor overall survival of prostate cancer patients [ 96 , 102 , 103 , 104 ]. This indicates an important role of SIRT6 in prostate cancer, which needs to be fully explored.…”

“…Furthermore, a recent study reported that SIRT6 promotes the progression of prostate cancer by abrogating necroptosis-facilitated innate immunity [ 96 ]. Another recent study also demonstrated that SIRT6 promotes the progression of prostate cancer by negatively regulating the Wnt/β-Catenin signaling pathway, as shown by a decrease in the expression levels of c-Myc, cyclin D1, and β-Catenin [ 104 ]. To date, all studies unequivocally portray SIRT6 as a promoter of prostate cancer.…”