Summary Research shows a higher incidence of colorectal cancer in men. However, the molecular mechanisms for this gender disparity remain unknown. We report the roles of androgen in proliferation and differentiation of intestinal stem cells via targeting of the androgen receptor (AR) on intestinal stromal cells by negatively regulating BMP signaling. Orchidectomy (ORX) or the AR antagonist promotes expansion of intestinal epithelium but suppresses intestinal stem cell (ISC) proliferation. Conversely, the AR agonist inhibits ISC differentiation but augments proliferation in ovariectomized mice. Mechanistically, activation of the AR increases expression of BMP antagonists but lowers expression of BMP4 and Wnt antagonists in primary stromal cells, which promotes intestinal organoid growth. Interestingly, the BMP pathway inhibitor LDN-193189 reverses the ORX-induced effects. Our results highlight that stromal cells constitute the intestinal stem cell niche and provide a possible explanation for higher incidence rates of colorectal cancer in men.

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Thyroid cancer (TC) is a common and curable endocrine tumor occurring in the head and neck characterized by a low mortality rate compared to other malignancies. in this study, the immune microenvironment of TC was investigated to identify biomarkers. The mRna and clinical data available in this study were accessed from The Cancer Genome atlas-Thyroid Cancer (TCGa-THCa) dataset. differences in immune infiltration levels of TC and normal samples were assessed by CibERSoRT. Thyroid cancer samples were classified into high-and low-abundance groups according to the median abundance of immune cell infiltration, and Cd8 + T cells were notably correlated with the survival status. differential expression analysis was conducted on Cd8 + T cells to obtain immune-related differentially expressed genes (dEGs). Subsequently, a prognostic risk model was established through Cox regression analysis. according to the median risk score, samples in the training set and validation set were assigned to high-and low-risk groups. The survival and RoC curves demonstrated that the model possesses favorable prognostic prediction ability. Furthermore, the results of gene set enrichment analysis (GSEa) indicated differences between the high-and low-risk groups in terms of ECM receptor interaction and transforming growth factor β (TGF-β) signaling pathways. The tumor microenvironment of TC samples was evaluated by ESTiMaTE, which showed that stromal scores were higher in the high-risk group. Finally, simple-sample GSEa (ssGSEa) was performed on TC samples. The results indicated a higher infiltration level of nK cells in the low-risk group, as well as a lower level in the high-risk group. in terms of immune function-related gene sets, genes related to aPC co-inhibition, cytolytic activity, HLa and T cell co-inhibition were observed to present higher expression levels in the low-risk group. in general, this study built a 6-gene prognostic risk assessment model based on Cd8 + T cells through bioinformatics analysis, which is expected to be a reference for clinicians to judge the prognosis of TC patients.

We aimed to examine the roles of microRNA-873-5p and CXCL5 in thyroid cancer (TC) cells. qRT-PCR was adopted to measure the expression levels of CXCL5 mRNA and microRNA-873-5p in TC cells, and western blot was adopted to evaluate the CXCL5 protein expression level. Bioinformatics analysis was done to predict the upstream gene of CXCL5. Dual-luciferase assay was applied to validate the binding relationship of CXCL5 and the upstream regulatory gene. Cell experiments were done to detect the effects of microRNA-873-5p targeting CXCL5 on malignant progression of cancer cells. Western blot was adopted to demonstrate the phosphorylation level of P53 pathway related-proteins. CXCL5 was upregulated in TC cells and tissues. The results of in vitro assays displayed that CXCL5 downregulation dramatically suppressed the malignant behaviors of TC cells. MicroRNA-873-5p suppressed CXCL5 expression, but the suppressive effect of microRNA-873-5p on TC cells was abolished through CXCL5 overexpression. Additionally, microRNA-873-5p could mediate p53 pathway and thereby inhibit the malignant behaviors of TC cells through targeting CXCL5. In summary, we proved that microRNA-873-5p repressed the malignant behaviors of TC cells through targeting CXCL5 and P53 pathway, indicating that microRNA-873-5p can be a biomarker for TC.

circRNA_0000140 on the growth and metastasis of oral squamous cell carcinoma [11]. MicroRNA-146b-5p hampers metastasis and tumourigenesis of gallbladder cancer by targeting Toll-like receptor 4 via the nuclear factor-κB pathway [12]. MicroRNA-133b can suppress colorectal cancer metastasis by lncRNA LUCAT1 [13]. MicroR-NA-196a-5p is a conserved microRNA derived from its precursor . MicroRNA-196a-5p has been studied in diseases including non-small cell lung cancer [15], cataracts [16], and gastric cancer [17]. However, in TC, the effect and specific mechanism of microR-NA-196a-5p remain unclear.Low-density lipoprotein receptor-associated protein 1 (LRP1) is a multifunctional receptor involved in many biological processes, including signal transduction, lipoprotein metabolism, regulation of vascular permeability and tension, cell growth, migration, and apoptosis [18]. LRP1B is a tumour suppressor that encodes LDL receptor [19]. LRP1B was originally discovered based on a homozygous deletion analysis in human lung cancer cell lines [20]. LRP1B is a member