Biology subjects

Chen, D.-M.

Publications and source records attributed to Chen, D.-M..

4 recordsLinked to original sources

bioRxiv2018

Dietary sulfate-driven and gut dysbiosis-triggered breast cancer-related gene upregulation

By gut microbiota metagenomic analysis, we found that the abundance of sulfatase-secreting bacteria (SSB) in the gut of mice fed chondroitin sulfate (CS) increases with significant individual difference. The fluctuation of lipopolysaccharide (LPS) and pro-inflammatory indicators with significant individual and tissue variations was also observed. After mice were fed mixed with CS or injected separately with LPS, the breast cancer-related transcriptional factor genes, BCL11A and RUNX1, were upregulated, whereas the tumor suppressor gene, TP53BP1, were downregulated. Further, the mammary myopithelium marker CK5/6, the mammary hyperplasia marker Ki-67, and other tumor markers were also upregulated. While the exogenous estradiol does not induce the expression of BCL11A, RUNX1, and TP53BP1, the estrogen receptor (ER) agonist Fulvestrant that mimics estradiol action not only elevates estradiol concentrations, but also upregulates tumor marker expression levels, revealing that ER inflammatory inactivation and hyperestrogenemia induction might be the etiological cues of breast cancer origin. This study has preliminarily established a possible correlation of gut microbiota dysbiosis and chronic low-grade inflammation with the early-phase onset of breast cancer in mice. The statistical insignificance of test data was attributed to the individual difference of gut microbiota compositions, which determining the individual and tissue variations of systemic inflammation.

cancer biology↗

bioRxiv2018

Spring mineral water-borne bacteria reshape gut microbiota profiles and confer health benefits

BackgroundAlthough dietary patterns are recognized to affect health by interfering with gut microbiota homeostasis, whether live or dead bacteria-bearing spring mineral water (MW) would also exert beneficial effects on health upon curing gut dysbiosis remains unknown.\n\nResultsDue to harboring live bacteria, the heated but unboiled MW from Bama, where centenarians are ubiquitously inhabited, reshapes the gut microbiota from a traveler-type to a local resident-type except for Prevotella. While chondroitin sulfate, a component occurring in livestock and poultry meats, increases the richness of sulfatase-secreting bacteria and sulfate-reducing bacteria, Bama MW dampens the overgrowth of those colon-thinning bacteria and hampers the overexpression of multiple genes responsible for anti-inflammation, anti-oxidation, anti-hypoxia, anti-mutagenesis, and anti-tumorigenesis.\n\nConclusionsBama spring MW prevents the early-phase onset of breast cancer by curating gut dysbiosis. MW also compromises chromosomal DNA damage and ameliorate mitochondrial dysfunctions, implying it may extend lifespan.

microbiology↗

bioRxiv2018

Reversal of microRNA-blocked tumor suppressors by biphenyl- dicarboxylate impedes endotoxin-induced hepatic hyperplasia

Hepatocellular carcinoma (HCC) is one of the most common malignant tumor and the leading cause of cancer-related death worldwide. Biphenyldicarboxylate (BPDC), an intermediate of schisandrin C from Schisandra chinensis, has been used as a hepatoprotective agent that compromises hepatic injuries in China for decades. Whether BPDC is also implicated in the prevention of HCC remains understood. Here, we report that the bacterial endotoxin lipopolysaccharide (LPS) promotes hepatic inflammation and hyperplasia, during which the common tumor markers, alpha fetoprotein (AFP) and carcinoembryonic antigen (CEA), were unregulated, whereas the tumor suppressors, PTEN, FOXO1 and MEN1, were downregulated through increasing the microRNAs, miR-21, miR-122 and miR-24. In contrast, BPDC dampened hepatic inflammation and hyperplasia accompanied by the upregulation of PTEN, FOXO1 and MEN1 through decreasing miR-21, miR-122 and miR-24. However, BPDC failed to downregulate the tumor marker AEG-1 via increasing miR-195. Taken together, BPDC exerts anti-tumor effects by upregulating tumor suppressors upon decreases of miRNAs rather than downregulating tumor markers by increases of miRNAs.

cancer biology↗

bioRxiv2018

Short-hairpin RNA-guided single gene knockdown reverses triple-negative breast cancer

BackgroundThe origin of breast cancer remains poorly understood. Here, we testify a putative mechanism of \"breast cancer origin from inducible nitric oxide synthase (iNOS) activation and oestrogen receptor alpha (ER) inactivation\", which are classified as the essential outcomes of chronic inflammatory responses.\n\nMethodsTo reverse breast cancer status, iNOS was downregulated by short-hairpin RNA (shRNA)-guided NOS2 knockdown from human triple-negative breast cancer (TNBC) cells. To re-enact breast cancer origin, ER was downregulated by shRNA-directed ESR1 knockdown in human mammary epithelial cells.\n\nResultsUpon NOS2 knockdown from HCC1937 cells, the specific TNBC transcription factor genes, RUNX1 and BCL11A, were downregulated, hypoxia was compromised, Warburg effects were attenuated, and tumourigenic proliferation was halted, accompanied by an increase in the tumour marker cyclin D1 (CD1) and a decrease in the tumour suppressor cyclin-dependent kinase inhibitor (CKI). In contrast, ESR1 knockdown from MCF-10A cells led to upregulated BCL11A and RUNX1 expression, augmented hypoxic responses, pronounced Warburg effects, and enhanced PI3K/Akt/mTOR signalling, together with low levels of CD1 and high levels of CKI induction.\n\nConclusionsBreast cancer should originate from inflammatory signalling, during which iNOS activation and ER inactivation elicit hypoxia, oxidation, mitochondrial dysfunction, and breast cancer-like hyperplasia, demonstrating that iNOS inhibitors and ER activators represent promising candidate prodrugs enabling breast cancer prevention in the early stage.

cancer biology↗