Chemokine receptors express on many tumor cells, and closely correlate with migration and metastasis of tumor cells. This study was to investigate expressions of chemokine(C-X-C) receptor 4 (CXCR4) and chemokine (C-X-C motif) ligand 12 (CXCL12) in human ovarian epithelial tumor cells, and their effects on migration of tumor cells.Expression of CXCR4 mRNA and protein in 15 specimens of epithelial ovarian cancer tissue, ovarian cancer cell line CAOV3, endothelial cell line HUVEC, and 10 specimens of normal ovary tissue were evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot. Expression of CXCL12 mRNA in retroperitoneal lymph nodes, and smooth muscle of fallopian tube from the same 15 epithelial ovarian cancer patients was tested by RT-PCR, quantity of CXCL12 in ascites of 15 patients was assayed using ELISA. Boyden Transwells was used to analyze effects of CXCL12, and cancerous ascites on chemotaxis of CAOV3, and HUVEC cells.(1) Expression levels of CXCR4 mRNA in ovary cancer tissues, CAOV3 cells, and HUVEC cells were 2.30+/-1.12, 1.89+/-1.20, and 1.68+/-1.11, respectively; those of CXCR4 protein were 1.35+/-0.14, 1.86+/-0.34, and 1.96+/-0.23, respectively; CXCR4 mRNA and protein can't be detected in normal ovarian tissues. (2) In 15 ovarian cancer patients, concentrations of CXCL12 in ascites were 632-9 326 pg/ml, and CXCL12 mRNA level in retroperitoneal lymph nodes was 1.14+/-0.87, CXCL12 mRNA can't be detected in smooth muscle of fallopian tube. (3) Recombinant human CXCL12 induced migration of CAOV3, and HUVEC cells, the chemotactic indices (CI) were 3.9+/-1.2, and 4.1+/-1.6, significantly higher than those of control (1.0+/-0.4, and 1.1+/-0.7) (P<0.05)u cancerous ascites induced migration of CAOV3 cells with CI of 1.9+/-0.8, significantly higher than that of control (P<0.05).CXCR4 and CXCL12 may play roles in metastasis of epithelial ovarian cancer by promoting migration of tumor cells and endothelial cells.
Abstract Background: Intriguingly, microRNA-20a (miR-20a) has been recently witnessed to be involved in the pathogenesis of endometriosis (EMS) but the molecular mechanism controlled by miR-20a is to be undefined. The present study is designed to probe into how miR-20a acts to regulate the cytotoxicity of natural killer (NK) cells. Methods: Most of all, consistent with the clinical determination in EMS patients, miR-20a was determined to be down-regulated in NK cells isolated from nude mice. miR-20a could specifically bind to ERG and negatively regulates its expression in NK cells. Additionally, shRNA-mediated silencing of ERG decreased the expression of HLX. HLX up-regulated STAT4 by inducing proteasome degradation and inhibited NK cell cytotoxicity. Results: Of great importance, forced expression of miR-20a consequently induced NK cell cytotoxicity in vitro by increasing perforin expression via enhancement of STAT4 that was caused by impairing the binding of ERG to HLX enhancer. The in vivo experiments further confirmed the promoting role of miR-20a in the cytotoxicity of NK cells isolated from EMS nude mice and subsequent protective role of miR-20a against EMS-induced endometrial injury. Conclusion: The aforementioned data suggest that miR-20a potentiates the cytotoxicity of NK via up-regulating perforin mediated by ERG/HLX/STAT4, highlighting potential novel mechanisms associated with EMS progression.
In this study, the complete mitochondrial genome (mitogenome) sequence of Pholis nebulosus has been determined by long polymerase chain reaction and primer-walking methods. The mitogenome is a circular molecule of 16 524 bp in length, including the typical structure of 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and 2 non-coding regions (L-strand replication origin and control region), the gene contents of which are identical to those observed in most bony fishes. Within the control region, we identified the termination-associated sequence domain (TAS), and the conserved sequence block domain (CSB-F, CSB-E, CSB-D, CSB-C, CSB-B, CSB-A, CSB-1, CSB-2, CSB-3).
Endometriosis is an estrogen-dependent gynecological disease primarily affecting women of childbearing age, which gives rise to pelvic pain calling for multiple operations, and sometimes leading to infertility. However, the etiology of endometriosis remains poorly understood. In this study we investigated the roles of two Ubiquitin E3 Ligases, namely hsc70-interacting protein (CHIP) and mouse double minute 2 (MDM2), in the abnormal estrogenic activity in endometriosis. We first collected endometrial tissues from 91 cases of endometriosis and 78 cases of uterine myomas. Next, we established a murine endometriosis model by ectopic endometrial tissue implantation. In other studies, we isolated human endometrial stromal cells (HESCs) were isolated from the endometrial tissues, and performed HA- or FLAG-immunoprecipitation assays and immunoblotting with an anti-ubiquitin antibody to test the interactions among BAG2, CHIP, MDM2, estrogen receptor α (ERα), and ERβ. The expression of ERα was downregulated while that of ERβ, BAG2, and MDM2 was upregulated in human endometriosis and in the mouse model. CHIP degraded ERβ instead of ERα via the ubiquitin-proteasome pathway, while BAG2 impaired the CHIP-mediated degradation of ERβ in cultured HESCs derived from human endometriosis. The degradation of ERα by MDM2 in cultured endometriosis-HESCs also occurred through the ubiquitin-proteasome pathway. Knockdown of both BAG2 and MDM2 alleviated the development of endometriosis in mice. Our findings suggest that the interference of BAG2 and MDM2 may have therapeutic effects in endometriosis. Understanding better the molecular mechanisms underlying the regulation of the abnormal estrogenic activity in endometriosis is crucial for the advancement of targeted therapeutic strategies.
Purpose: Since deterioration of the immune apparatus is closely associated with cancer, we examined the effect of aging on the growth and metastasis of intraocular melanomas in mice. Methods: Murine B16LS9 melanoma cells were transplanted into the posterior compartment of the eye (vitreous chamber) and intraocular tumor growth and development of liver metastases were evaluated in young (8–10 weeks of age) and old (>18 months of age) mice. Liver metastases were also induced by intrasplenic injection of melanoma cells. Natural killer (NK) cells from the livers of mice harboring liver metastases were evaluated in vitro for their cytolytic activity. Results: Tumors grew more rapidly in the eyes of young mice than old mice, yet old mice developed significantly more liver metastases. Increased liver metastasis in old mice was evident even when melanoma cells were injected intrasplenically as a means of bypassing the influence of the ocular immunosuppressive environment. Increased liver metastases in old mice correlated with reduced cytolytic activity of liver NK cells. Lethally irradiated young mice reconstituted with bone marrow from old donors developed significantly more liver metastases than young mice reconstituted with bone marrow from young donors, indicating that bone marrow–derived cells were the root cause of the heightened development of metastases in old mice. Conclusions: Aging affects the growth and metastasis of intraocular melanomas. Even though intraocular melanomas grow slower in old mice, the development of liver metastases is exacerbated and correlates with a reduction in liver NK cell activity in the old mouse.
Two similar cardinalfish species, Jaydia striatodes and J. striata, were compared morphologically and genetically, using the fragment of cytochrome oxidase subunit I (COI) gene of the mitochondrial DNA. The results confirmed the validity of both species and their sister group relationship. The species formed well-supported monophyletic clades that were distinctly separate with mean sequence divergence of 12.2%. Jaydia striatodes is distinct in having 4–5 + 12–13 gill rakers; 3 + 11–12 developed gill rakers; 9 gill rakers on the first ceratobranchial; 3–9 weak serration at the angle of preopercular edge; and a usually blackish distal half of anal fin. Jaydia striatodes was recorded for the first time from Beibu Gulf, China, and from Vietnam.
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