Helicobacter pylori (H pylori) is the main risk factor for gastric cancer (GC). In recent years, many studies have addressed the effects of H pylori itself and of H pylori-induced chronic inflammation on DNA damage. Unrepaired or inappropriately repaired DNA damage is one possible carcinogenic mechanism. We may conclude that H pylori-induced DNA damage is one of the carcinogenic mechanisms of GC. In this review, we summarize the interactions between H pylori and DNA damage and the effects of H pylori-induced DNA damage on GC. Then, focusing on oxidative stress, we introduce the application of antioxidants in GC. At the end of this review, we discuss the outlook for further research on H pylori-induced DNA damage.
K E Y W O R D SDNA damage, Helicobacter pylori, NF-κB, PLK
N6-Methyladenosine (m6A), one of the post-transcriptional modifications of RNA, is important in hepatocellular carcinoma (HCC). However, the mechanism of its regulation remains elusive. We here show that exposure of HCC cells to sulfatide significantly reduced the total mRNA m6A modification. Interestingly, METTL3 protein was robustly acetylated and the binding of METTL3 to MTF1 mRNA, METTL14 or WTAP was weakened in cells treated with sulfatide. Further investigation of the METTL3 complex revealed recruitment of the deacetylase scaffold SIN3B, but a diminished level of histone deacetylase HDAC2, which might enhance the acetylation of METTL3. The m6A abundance in MTF1 mRNA was markedly decreased in cells after sulfatide treatment. The expression of MTF1, a zinc-dependent transcription factor, was significantly strengthened with reduced m6A modification. Sulfatide prolonged the half-life of MTF1 mRNA, while the mutation (A to C) on 7 methylation sites in the 3'UTR of MTF1 mRNA enhanced MTF1 mRNA stability. 3-deaza-adenosine, an m6A methylation inhibitor, significantly reduced the m6A modification of MTF1 mRNA but extended its half-life time. Importantly, overexpression of MTF1 prompted HCC cell proliferation and was associated with poor prognosis. In conclusion, the METTL3-METTL14-WTAP complex was regulated by acetylation induced by sulfatide to control MTF1 m6A methylation and its mRNA transcription, which was important for the tumor growth and migration of HCC.
Background and Aim
Radiation therapy (RT) is a crucial modality for the local control of esophageal cancer (EC), but the effect of RT on the development of secondary thoracic malignancies is still unclear. This study aims to identify the association between RT for the treatment of primary EC and subsequent secondary thoracic cancer (STC).
Methods
The primary EC patients were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Fine‐Gray competing risk regression and standardized incidence ratio (SIR) were used to evaluate the radiotherapy‐associated cancer risk. Overall survival (OS) was compared by Kaplan–Meier analysis.
Results
A total of 40 255 EC patients from the SEER database were identified, of which 17 055 patients (42.37%) did not receive radiotherapy (NRT) and 23 200 patients (57.63%) had been treated with RT. After 12 months of latency, 162 patients (0.95%) in the NRT group and 272 patients (1.17%) in the RT group developed STC. The incidences of the RT group were significantly higher than the NRT group. Patients who have primary EC were at an increased risk of developing STC (SIR = 1.79, 95% CI: 1.63–1.96). The SIR of STC was 1.37 (95% CI: 1.16–1.60) in the NRT group and 2.10 (95% CI: 1.87–2.34) in the RT group. The OS of STC patients in the RT group was significantly lower than the NRT group (P = 0.006).
Conclusion
The RT for primary EC was associated with higher risks of developing STC than patients unexposed to radiotherapy. The EC patients treated with RT, especially young patients, require long‐term monitoring of the risk of STC.
Gastric cancer (GC) is one of the most common causes of cancer-related death worldwide, and gastric cancer stem cells (GCSCs) are considered as the major factor for resistance to conventional radio- and chemotherapy. Accumulating evidence in recent years implies that GCSCs regulate the drug resistance in GC through multiple mechanisms, including dormancy, drug trafficking, drug metabolism and targeting, apoptosis, DNA damage, epithelial-mesenchymal transition, and tumor microenvironment. In this review, we summarize current advancements regarding the relationship between GCSCs and drug resistance and evaluate the molecular bases of GCSCs in drug resistance.
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