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Single-cell analyses unravel cell type-specific responses to a vitamin D analog in prostatic precancerous lesions.

ABSTRACT: Epidemiological data have linked vitamin D deficiency to the onset and severity of various cancers, including prostate cancer, and although in vitro studies have demonstrated anticancer activities for vitamin D, clinical trials provided conflicting results. To determine the impact of vitamin D signaling on prostatic precancerous lesions, we treated genetically engineered Pten^(i)pe-/- mice harboring prostatic intraepithelial neoplasia (PIN) with Gemini-72, a vitamin D analog with reported anticancer activities. We show that this analog induces apoptosis in senescent PINs, normalizes extracellular matrix remodeling by stromal fibroblasts, and reduces the prostatic infiltration of immunosuppressive myeloid-derived suppressor cells. Moreover, single-cell RNA-sequencing analysis demonstrates that while a subset of luminal cells expressing Krt8, Krt4, and Tacstd2 (termed luminal-C cells) is lost by such a treatment, antiapoptotic pathways are induced in persistent luminal-C cells. Therefore, our findings delineate the distinct responses of PINs and the microenvironment to Gemini-72, and shed light on mechanisms that limit treatment's efficacy.

SUBMITTER: Abu El Maaty MA

PROVIDER: S-EPMC8324049 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Single-cell analyses unravel cell type-specific responses to a vitamin D analogue in prostatic precancerous lesions

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-08-04 | GSE164858 | GEO

Single-cell analyses unravel cell type-specific responses to a vitamin D analogue in prostatic precancerous lesions [scRNA-Seq]

Project description:Epidemiological data have linked vitamin D deficiency to the onset of various cancers, including prostate cancer, and although in-vitro studies have demonstrated anti-cancer activities for the vitamin, clinical trials provided conflicting results. To determine the impact of vitamin D signaling on prostatic precancerous lesions, we treated genetically-engineered mice harboring prostatic intraepithelial neoplasia (PIN) with Gemini-72, a vitamin D analogue with reported anti-cancer activities, and comprehensively analyzed its effects on various cell types in such lesions. We show that this analogue induces apoptosis in senescent PINs and normalizes extracellular matrix remodeling by stromal fibroblasts in an epithelial VDR-dependent manner. Furthermore, it reduces the prostatic infiltration of immunosuppressive myeloid-derived suppressor cells in an epithelial VDR-independent manner. Moreover, single-cell RNA-sequencing analysis demonstrates that while a subset of luminal epithelial cells, expressing Krt4 and Tacstd2 (termed luminal-C) with enhanced interferon signature, is lost by such a treatment, anti-apoptotic pathways are induced in persistent luminal-C cells. Therefore, our findings delineate the distinct responses of prostatic precancerous lesions and the microenvironment to the vitamin D analogue, and shed light on mechanisms that limit treatment’s efficacy.

2021-08-04 | GSE164856 | GEO

Single-cell analyses unravel cell type-specific responses to a vitamin D analogue in prostatic precancerous lesions [RNA-Seq]

Project description:We treated PTENpe-/- mice, in which PTEN is selectively ablated in prostatic epithelial cells, with a Vitamin D analog. We extracted RNA from the prostate of oil (vehicle) and Vitamin D analog-treated mice.

2021-08-04 | GSE164855 | GEO

Single-cell analyses unravel cell type-specific responses to a vitamin D analogue in prostatic precancerous lesions

Project description:Single-cell analyses unravel cell type-specific responses to a vitamin D analogue in prostatic precancerous lesions

| PRJNA692208 | ENA

Single-cell analyses unravel cell type-specific responses to a vitamin D analogue in prostatic precancerous lesions [RNA-Seq]

Project description:Single-cell analyses unravel cell type-specific responses to a vitamin D analogue in prostatic precancerous lesions [RNA-Seq]

| PRJNA692210 | ENA

Single-cell analyses unravel cell type-specific responses to a vitamin D analogue in prostatic precancerous lesions [scRNA-Seq]

Project description:Single-cell analyses unravel cell type-specific responses to a vitamin D analogue in prostatic precancerous lesions [scRNA-Seq]

| PRJNA692211 | ENA

Single-cell and spatial dissection of precancerous lesions underlying the initiation process of oral squamous cell carcinoma

Project description:Precancerous lesions of the oral mucosa, especially those accompanied by moderate to severe dysplasia, contribute to the initiation of oral squamous cell carcinoma (OSCC). However, the cellular compositions and spatial organization of the precancerous stage and how these factors promote human OSCC initiation remain unclear. Here, we built a single-cell transcriptome atlas and a spatial transcriptome map after obtaining data from pairwise human oral mucosal biopsies of 9 individuals consisting of very early-stage OSCC, adjacent precancerous lesions with moderate to severe dysplasia, as well as a matched normal region. An altered epithelial gene-expression profile was identified which favored OSCC initiation. This observation was coupled with distinct fibroblast, monocytic, and regulatory T-cell subclusters involved in reshaping the microenvironment. In particular, a unique immune-inhibitory monocyte subtype and spatial-switching regulation of VEGF signaling were observed surrounding precancerous lesions, concertedly strengthening activities in promoting cancer initiation. Collectively, our work elucidated the cellular landscapes and roles of precancerous lesions underlying OSCC initiation, which is essential for understanding the entire OSCC initiation process and helps inform therapeutic strategies for cancer intervention.

| S-EPMC10011538 | biostudies-literature

Thyroid cancer: tumor vs. precancerous lesions

Project description:Multiple lines of evidence have highlighted that long noncoding RNAs (lncRNAs) serve as a novel class of regulators of cancer biological processes. Currently, our knowledge of lncRNAs in papillary thyroid carcinoma (PTC) is still limited. Using microarray analysis, we identified a lncRNA (lncAB), which is downregulated in PTC. The decreased expression of lncAB is induced by CpG hypermethylation in the flanking region of lncAB. Overexpression of lncAB inhibited tumor growth and arrested G2/M phase in vitro and in vivo, whereas knockdown of lncAB promoted cell proliferation, colony formation, DNA replication ability, and increased G0/G1 phase. Mechanistic analyses revealed that lncAB binds to KHSRP, resulting in the mRNA degradation, high expression of CDKN1a and low expression of CDK2, and thereby repressed cell proliferation. Taken together, we provide evidence that lncAB is a tumor suppressor in PTC tumorigenesis and delineate a novel mechanism of lncRNA in PTC progression.

2017-08-30 | GSE103254 | GEO

Treatment of gastric precancerous lesions with Weiansan.

Project description:AimTo observe the curative effect of Weiansan (WAS) on gastric precancerous lesions (GPL) and H pylori elimination.MethodsSeventy-six patients with GPL were randomly divided into two groups: WAS group (n = 42) and Weifuchun (WFC) group (n = 34). The patients in the WAS group were administered 5 g WAS 3 times a day, and the patients in the WFC group took WFC (4 tablets) 3 times a day. To monitor inflammation of gastric mucosa, degree of glandular atrophy (GA), intestinal metaplasia (IM) and dysplasia, and H pylori infection, all patients underwent gastroscopy and biopsy with pathological examination before and after treatment. Fifty male Sprague-Dawley (SD) rats were used in animal experiments. Of these, 10 served as the control group (n = 10), 40 were given ranitidine combined with N-methyl-N(1)-nitro-N-nitrosoguanidine (MNNG) for 12 wk and divided into 4 groups randomly: model group (n = 10), high-dose WAS group (n = 10), low-dose WAS group (n = 10) and WFC group (n = 10). Twelve weeks later, all rats were killed and a 2 cm multiply 1 cm tissue was taken from the lesser curvature of the gastric antrum. H pylori infection was determined by the fast urease method.ResultsThe curative effect in WAS groups was similar to that in WFC groups. There was no statistical difference in degree of GA, IM and dysplasia between WAS and WFC groups. The rate of H pylori infection in the model group (positive/negative: 9/1) was significantly higher than that in the control group (positive/negative: 1/9) (P < 0.01). H pylori elimination in the high-dose WAS group (positive/negative: 4/6) and low-dose WAS group (positive/negative: 6/4) was similar to that in the WFC group (positive/negative: 4/6) (P > 0.05).ConclusionWAS improves clinical symptoms by suppressing GA, IM and dysplasia and eliminating H pylori.

| S-EPMC4088211 | biostudies-literature

Association between oral health and gastric precancerous lesions.

Project description:Although recent studies have suggested that tooth loss is positively related to the risk of gastric non-cardia cancer, the underlying oral health conditions potentially responsible for the association remain unknown. We investigated whether clinical and behavioral measures of oral health are associated with the risk of gastric precancerous lesions. We conducted a cross-sectional study of 131 patients undergoing upper gastrointestinal endoscopy. Cases were defined as those with gastric precancerous lesions including intestinal metaplasia or chronic atrophic gastritis on the basis of standard biopsy review. A validated structured questionnaire was administered to obtain information on oral health behaviors. A comprehensive clinical oral health examination was performed on a subset of 91 patients to evaluate for periodontal disease and dental caries experience. A total of 41 (31%) cases of gastric precancerous lesions were identified. Compared with non-cases, cases were significantly more likely to not floss their teeth [odds ratio (OR) = 2.89, 95% confidence interval (CI): 1.09-7.64], adjusting for age, sex, race, body mass index, smoking status, educational attainment and Helicobacter pylori status in serum. Among participants who completed the oral examination, cases (n = 28) were more likely to have a higher percentage of sites with gingival bleeding than non-cases [OR = 2.63, 95% CI: 1.37-5.05 for a standard deviation increase in bleeding sites (equivalent to 19.7%)], independent of potential confounders. Our findings demonstrate that specific oral health conditions and behaviors such as gingival bleeding and tooth flossing are associated with gastric precancerous lesions.

| S-EPMC3384024 | biostudies-literature

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