Volume 37, Issue 2, February 2016

SIRT6 regulates diverse cellular functions such as transcription, genome stability, telomere integrity, DNA repair, inflammation and metabolic-related diseases such as diabetes and obesity. In this review, we will discuss the role of SIRT6 in cancer via regulating the above-mentioned functions.

Jumonji domain-containing protein 6 (JMJD6) is positively associated with oral carcinogenesis and enriched in oral cancer stem cells (CSCs). JMJD6 is a novel regulator of oral CSC phenotype and promotes self-renewal in part via upregulating the expression of interleukin 4.

Our findings demonstrated that DNA lesions that induce major helix distortion only form in euchromatin, and SIRT1 plays a critical role in restricting the formation of this kind of DNA lesions in cells.

Whole-exome sequencing with follow-up genotyping of selected variants identifies an association with lung cancer subphenotyped for emphysema. Our analysis highlights differences in genetic background among lung cancer cases with or without emphysema.

We have synthesized and characterized a novel DNA crosslinking agent VDC which can be activated by visible light. VDC induces high degree of cell death in HR/ICL repair defective cancer cells and hence can be potentially used for cancer therapy.

Lung adenocarcinomas with L858R mutation, rather than exon 19 deletion, preferentially occur in upper lobes. This might be partially explained by the same reason that inhaled noxious agents or pathogens usually cause upper lung diseases.

The association between the 6q25.1 locus and breast cancer risk may be mediated through SNPs that regulate expressions of the AKAP12 gene. SNP rs7763637, in strong LD with rs2046210, is a potential functional variant at the 6q25.1 locus.

We revealed that the MGMT rs34180180 SNP is associated with aggressive glioma patients’survival. Our study suggests that a simple genetic test at this SNP could improve the prognostic value of the MGMT promoter methylation assay and may help to individualize clinical decision-making.

Following acute exposure to crocidolite asbestos fibers, flaxseed lignans, enriched in secoisolariciresinol diglucoside (SDG), significantly reduced peritoneal inflammation, proinflammatory/profibrogenic cytokine release and oxidative/nitrosative stress in mice. Our findings support the potential role of SDG, which is safe and well-tolerated, in the chemoprevention of malignant mesothelioma.

The relationship between chromosomal instability and integration of the human papillomavirus (HPV) DNA into the host genome is not well understood. We found that chromosomal instability increases with HPV integration and diagnosis. However, chromosomal instability could occur without HPV integration.

Cancer cells potentially escape cell death through the IL-8/CXCR1 survival-signaling pathway. We discovered that IL-32 splice variants possess different functions in inducing cell death in this pathway. Modulation of IL-32 alternative splicing could represent a novel anticancer strategy.

Colonic Lgr5 ⁺ stem cells are highly susceptible to AOM-induced DNA damage and actively induce damage repair enzyme expression and untargeted apoptosis.

Nuclear EGFR induced PPARγ–Y74 residue phosphorylation. PPARγ/Y74 phosphorylation was required for ubiquitination and degradation by MDM2 ubiquitin ligase. PPARγ degradation promoted EGFR/NF-κB-signaling-mediated cell proliferation and survival in response to chemotherapeutic agents.