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Published on: January 22, 2021
Tumour-suppressive function of SIRT4 in human colorectal cancer
M Miyo1, H Yamamoto1, M Konno2
1Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.
Background:
SIRT4, which is localised in the mitochondria, is one of the least characterised members of the sirtuin family of nicotinamide adenine dinucleotide-dependent enzymes that play key roles in multiple cellular processes such as metabolism, stress response and longevity. There are only a few studies that have characterised its function and assessed its clinical significance in human cancers.
Methods:
We established colorectal cancer cell lines (SW480, HCT116, and HT29) overexpressing SIRT4 and investigated their effects on proliferation, migration and invasion, as well as E-cadherin expression, that negatively regulates tumour invasion and metastases. The associations between SIRT4 expression in colorectal cancer specimens and clinicopathological features including prognosis were assessed by immunohistochemistry.
Results:
SIRT4 upregulated E-cadherin expression and suppressed proliferation, migration and invasion through inhibition of glutamine metabolism in colorectal cancer cells. Moreover, SIRT4 expression in colorectal cancer decreased with the progression of invasion and metastasis, and a low expression level of SIRT4 was correlated with a worse prognosis.
Conclusions:
SIRT4 has a tumour-suppressive function and may serve as a novel therapeutic target in colorectal cancer.
Insights
SIRT4, a mitochondrial enzyme, suppresses colorectal cancer growth and metastasis by upregulating E-cadherin and inhibiting glutamine metabolism. Low SIRT4 expression correlates with poor prognosis, suggesting its potential as a therapeutic target.
Area of Science:
- Mitochondrial biology
- Cancer research
- Enzymology
Background:
- SIRT4 is a poorly characterized mitochondrial sirtuin involved in cellular processes.
- Limited studies exist on SIRT4's function and clinical significance in human cancers.
Purpose of the Study:
- To investigate the role of SIRT4 in colorectal cancer (CRC) progression.
- To assess SIRT4's potential as a therapeutic target in CRC.
Main Methods:
- Overexpression of SIRT4 in colorectal cancer cell lines (SW480, HCT116, HT29).
- Assessed effects on proliferation, migration, invasion, and E-cadherin expression.
- Immunohistochemistry used to correlate SIRT4 expression with clinicopathological features and prognosis in CRC specimens.
Main Results:
- SIRT4 overexpression suppressed proliferation, migration, and invasion.
- SIRT4 upregulated E-cadherin expression and inhibited glutamine metabolism.
- Decreased SIRT4 expression correlated with advanced invasion/metastasis and worse prognosis in CRC patients.
Conclusions:
- SIRT4 exhibits tumor-suppressive functions in colorectal cancer.
- SIRT4 may serve as a novel therapeutic target for colorectal cancer treatment.
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