Inhibition of autophagy aggravates DNA damage response and gastric tumorigenesis via Rad51 ubiquitination in response to <i>H. pylori</i> infection

Xie, Chuan; Li, Nianshuang; Wang, Huan; He, Cong; Hu, Yi; Peng, Chao; Ouyang, Yaobin; Wang, Dejie; Xie, Yong; Jiang, Chen; Shu, Xu; Zhu, Yin; Lü, Nonghua

doi:10.1080/19490976.2020.1774311

Cited by 51 publications

(43 citation statements)

References 51 publications

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“…Our data showed that DCTPP1 silencing triggers DNA damage in BRCA cells, while its upregulation up-regulated the levels of DNA repair-associated factors, XRCC1, PARP1, and RAD51. DNA repair pathways are DNA damage response mechanisms ( 28 , 29 ). DNA repair pathways influence cell survival and are anti-cancer therapeutic targets of radiotherapy and cytotoxic chemotherapy ( 30 , 31 ).…”

Section: Discussionmentioning

confidence: 99%

DCTPP1, an Oncogene Regulated by miR-378a-3p, Promotes Proliferation of Breast Cancer via DNA Repair Signaling Pathway

et al. 2021

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Breast cancer (BRCA) is one of the most deadly cancers worldwide, with poor survival rates that could be due to its high proliferation. Human all-alpha dCTP pyrophosphatase 1 (DCTPP1) is implicated in numerous diseases, including cancers. However, its role in BRCA is unclear. In this study, we used bioinformatic analyses of the ONCOMINE, UALCAN, and GEPIA databases to determine the expression pattern of DCTPP1 in BRCA. We found that elevated DCTPP1 levels correlate with poor BRCA prognosis. DCTPP1 silencing inhibited BRCA cell proliferation and induced apoptosis in vitro, as well as in vivo. Our data show that this tumorigenic effect depends on DNA repair signaling. Moreover, we found that DCTPP1 is directly modulated by miR-378a-3p, whose downregulation is linked to BRCA progression. Our results showed down-regulation of miR-378a-3p in BRCA. Upregulation of miR-378a-3p, on the other hand, can inhibit BRCA cell growth and proliferation. This study shows that reduced miR-378a-3p level enhances DCTPP1 expression in BRCA, which promotes proliferation by activating DNA repair signaling in BRCA.

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Section: Discussionmentioning

confidence: 99%

DCTPP1, an Oncogene Regulated by miR-378a-3p, Promotes Proliferation of Breast Cancer via DNA Repair Signaling Pathway

et al. 2021

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“…In protein–protein interactions, one study suggested that the relationship between RAD51 and autophagy is associated with checkpoint kinase 1 (CHK1) in an esophageal cancer model by inhibiting autophagy [ 22 ]. Thus, in several cancers, the inhibition of autophagy promotes DNA damage and a susceptibility to cancer treatment by the downregulation of RAD51 [ 23 , 24 , 25 ]. On the contrary, one study reported that inducing autophagy reduces RAD51 expression in non-small cell lung cancer (NSCLC) cell models [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

Epigenomic Analysis of RAD51 ChIP-seq Data Reveals cis-regulatory Elements Associated with Autophagy in Cancer Cell Lines

Kang

Choi

Moon

et al. 2021

Cancers

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RAD51 is a recombinase that plays a pivotal role in homologous recombination. Although the role of RAD51 in homologous recombination has been extensively studied, it is unclear whether RAD51 can be involved in gene regulation as a co-factor. In this study, we found evidence that RAD51 may contribute to the regulation of genes involved in the autophagy pathway with E-box proteins such as USF1, USF2, and/or MITF in GM12878, HepG2, K562, and MCF-7 cell lines. The canonical USF binding motif (CACGTG) was significantly identified at RAD51-bound cis-regulatory elements in all four cell lines. In addition, genome-wide USF1, USF2, and/or MITF-binding regions significantly coincided with the RAD51-associated cis-regulatory elements in the same cell line. Interestingly, the promoters of genes associated with the autophagy pathway, such as ATG3 and ATG5, were significantly occupied by RAD51 and regulated by RAD51 in HepG2 and MCF-7 cell lines. Taken together, these results unveiled a novel role of RAD51 and provided evidence that RAD51-associated cis-regulatory elements could possibly be involved in regulating autophagy-related genes with E-box binding proteins.

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“…Many of them (e.g., Flavonifractor , Enterorhabdus , Desulfovibrio , Elusimicrobium , Roseburia , Candidatus _ Saccharimonas , Anaerovorax , Caproiciproducens , Lachnoclostridium , Ruminiclostridium , Intestinimonas ) play a key role in immunity regulation and intestinal health ( Zhang et al, 2020a ; Zhang et al, 2020b ; Zhao, Jiang & Chu, 2020 ; Ward et al, 2017 ; Zhang et al, 2020a ; Zhang et al, 2020b ). However, Unidentified_Clostridiales , Oscillibacter , Anaerofilum , Parasutterella , Tyzzerella , Blautia , Peptococcus , Mycoplasma , Helicobacter , Butyricimonas have pathogenic and pro-inflammatory effects ( Xu et al, 2020 ; Xue et al, 2020 ; Xie et al, 2020 ). The change in their abundance of these bacteria with age may be a potential reason for the shorter life span (around one year) of Brandt’s voles in the wild.…”

Section: Discussionmentioning

confidence: 99%

Sex- and age-specific variation of gut microbiota in Brandt’s voles

Zhang

2021

PeerJ

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Background Gut microbiota plays a key role in the survival and reproduction of wild animals which rely on microbiota to break down plant compounds for nutrients. As compared to laboratory animals, wild animals face much more threat of environmental changes (e.g. food shortages and risk of infection). Therefore, studying the gut microbiota of wild animals can help us better understand the mechanisms animals use to adapt to their environment. Methods We collected the feces of Brandt’s voles in the grassland, of three age groups (juvenile, adult and old), in both sexes. We studied the gut microbiota by 16S rRNA sequencing. Results The main members of gut microbiota in Brandt’s voles were Firmicutes, Bacteroidetes and Proteobacteria. As voles get older, the proportion of Firmicutes increased gradually, and the proportion of Bacteroides decreased gradually. The diversity of the microbiota of juveniles is lower, seems like there is still a lot of space for colonization, and there are large variations in the composition of the microbiome between individuals. In adulthood, the gut microbiota tends to be stable, and the diversity is highest. In adult, the abundances of Christensenellaceae and Peptococcus of female were significantly higher than male voles. Conclusions The gut microbiota of Brandt’s vole was influenced by sex and age, probably due to growth needs and hormone levels. Gut microbiota of wild animals were much influenced by their life-history reflected by their age and sex. Future studies will be directed to identify functions of these “wild microbiota” in regulating physiological or behavioral processes of wild animals in different life stage or sexes.

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Inhibition of autophagy aggravates DNA damage response and gastric tumorigenesis via Rad51 ubiquitination in response to H. pylori infection

Cited by 51 publications

References 51 publications

DCTPP1, an Oncogene Regulated by miR-378a-3p, Promotes Proliferation of Breast Cancer via DNA Repair Signaling Pathway

DCTPP1, an Oncogene Regulated by miR-378a-3p, Promotes Proliferation of Breast Cancer via DNA Repair Signaling Pathway

Epigenomic Analysis of RAD51 ChIP-seq Data Reveals cis-regulatory Elements Associated with Autophagy in Cancer Cell Lines

Sex- and age-specific variation of gut microbiota in Brandt’s voles

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