SIRT4 acts as a tumor suppressor in gastric cancer by inhibiting cell proliferation, migration, and invasion

Abstract

BackgroundPrevious study has proven that SIRT4 is downregulated in gastric cancer (GC), but the role of SIRT4 has not been clearly understood. The aim of our work was to explore in detail the function and mechanism of SIRT4 in GC.MethodsA total of 86 pairs of GC tumor tissues and adjacent normal tissues were collected, and quantitative real-time polymerase chain reaction and Western blotting analyses were used to determine the expression of SIRT4.ResultsOur study revealed that the expression of SIRT4 was downregulated in GC tissues and cells. In addition, the low expression of SIRT4 was negatively correlated with tumor size, pathological grade, and lymph node metastasis, which predicted a poor prognosis. Multiple functional experiments, including Cell Counting Kit-8 assay as well as colony formation assay, demonstrated SIRT4 suppressed cell proliferation. Moreover, we found epithelial–mesenchymal transition was regulated by SIRT4, thereby regulating cell migration and invasion.ConclusionOverall, our findings show that SIRT4 serves as a tumor suppressor in GC and might act as a novel biomarker and a therapeutic target of GC.

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

“…As a consequence, the high mRNA expression levels of SIRT1 and SIRT4 were associated with an unfavorable prognosis in patients with OC. Similarly, previous studies have also verified the roles of the aforementioned two SIRTs in other carcinomas, such as lung cancer (30,31), breast cancer (32)(33)(34), gastric cancer (35,36), and prostate cancer (37). Specifically, Shin et al (30) reported that high SIRT1 expression was identified in non-small cell lung cancer, which was highly associated with drug resistance via the SIRT1-mitogen-activated protein kinase signaling pathway.…”

The Roles of Sirtuin Family Proteins in Cancer Progression

“…Apoptosis NSCLC [40] P53 CCA [41] MYC Metastasis HCC [42,43] AKT/GSK3β/β-catenin Axis GC [44] Tumorigenesis BC [45] Slug HCC [39] APC, CDC20 BC [39] APC, CDC20 SIRT3 Viability BLC [46] P53 PC [47] MYC; PI3K/AKT pathway CRC [48] AKT/PTEN NSCLC [49] Bax/Bcl-2, P53 HCC [50] PI3K/AKT pathway PDC [51] Apoptosis NSCLC [49] Bax/Bcl-2, P53 OSCC [52] RIP Leukemia [53] AKT, Bax/Bcl-2 Metastasis CRC [48] AKT/PTEN HCC [50] PI3K/AKT pathway PDC [51] PC [54] FOXO3A, Wnt/β-catenin pathway OC [55] Twist [57] ERK/Drp1 Axis ESCC [58] GDH CRC [59] GC [60] Apoptosis Metastasis NSCLC [57] ERK/Drp1 Axis ESCC [58] GDH CRC [59] E-cadherin GC [60] E-cadherin [72] COX-2, AKT, AMPK CRC [73] PTEN/AKT signaling ACC [74] NF-κB signaling GBM [75] JAK2/STAT3 pathway Apoptosis CRC [73] PTEN/AKT signaling HCC [70] Bax GBM [75] AK2/STAT3 pathway FSA [76] NF-κB signaling HCC [77,78] ERK1/2 pathway CC [76] NF-κB signaling Metastasis HCC [71,79] PKM2 CRC…”

“…SIRT4 also suppresses cell proliferation. It is responsible for the regulation of EMT, thereby regulating cell migration and invasion in GC [60].…”

The sirtuin family in cancer

“…SIRT4 was also found to be downregulated in human samples of gastric cancer, and this decrease was related to poor prognosis and survival [163,165,174]. In cell models, genetic ablation of SIRT4 induced cell growth and invasion in MKN-45 and HGC-27 gastric cancer cells [174].…”