LncRNA H19 over-expression inhibited Th17 cell differentiation to relieve endometriosis through miR-342-3p/IER3 pathway.

OBJECTIVE: To investigate the mechanism of LncRNA H19 in Th17 cell differentiation and endometrial stromal cells (ESCs) proliferation in endometriosis (EMS). METHODS: LncRNA H19, miR-342-3p and IER3 expressions were detected by qRT-PCR and western blot. The percentage of Th17 cells/CD4+ T cells was detected by flow cytometry. IL-17 level was measured by ELISA. The interaction of miR-342-3p and IER3 was confirmed by Luciferase reporter assay. RESULTS: LncRNA H19 and IER3 expressions were down-regulated in mononuclear cells from peritoneal fluid (PFMCs) of patients with EMS or under Th17 differentiation conditions, whereas miR-342-3p expression was up-regulated and the percentage of Th17 cells was increased in PFMCs of patients with EMS or under Th17 differentiation conditions. Over-expression of LncRNA H19 decreased IL-17 level and the percentage of Th17 cells/CD4+ T cells. Besides, we confirmed that miR-342-3p could target to IER3 and negatively regulate IER3 expression. LncRNA H19 over-expression suppressed Th17 differentiation and ESC proliferation through regulating miR-342-3p/IER3. In vivo experiments showed LncRNA H19 over-expression suppressed the growth of Th17 cell differentiation-induced endometriosis-like lesions. CONCLUSION: LncRNA H19 was down-regulated in PFMC of patients with EMS or under Th17 polarizing conditions, and LncRNA H19 over-expression suppressed Th17 cell differentiation and ESCs proliferation through miR-342-3p/IER3 pathway.

LncRNA GAS5 confers the radio sensitivity of cervical cancer cells via regulating miR-106b/IER3 axis.

OBJECTIVE: The aim of the study was to investigate the biological role of growth arrest special 5 (GAS5) in the radio sensitivity of cervical cancer (CC). METHODS: The expressions of GAS5, miR-106b and immediate early response 3 (IER3) were detected in CC tissues and CC cell lines. RNA immunoprecipitation and RNA pull-down assays were performed to test the interaction of GAS5 and miR-106b. Dual-luciferase reporter assay was used to detect the regulatory relationship between miR-106b and IER3. The nude mouse model of CC was established for verifying the effects of GAS5 on the resistance of CC to radiation therapy in vivo. RESULTS: GAS5 and IER3 were low expressed in the radio-resistant human CC tissues and SiHa cells, while miR-106b expression was highly expressed. Overexpression of IER3 or GAS5 enhanced radio-sensitivity in SiHa cells, while knockdown of IER3 or GAS5 decreased radio-sensitivity in ME180 cells. Moreover, GAS5 served as a miR-106b sponge, and miR-106b negatively regulated IER3 expression. Besides, GAS5 could regulate IER3 expression through miR-106b, and GAS5 enhanced the radio-sensitivity in CC cells through inhibiting miR-106b both in vitro and in vivo. CONCLUSION: Overexpression of GAS5 enhanced the sensitivity of CC cells to radiation treatment via up-regulating IER3 through miR-106b.

Significance of blood and salivary IEX-1 expression in diagnosis of epithelial ovarian carcinoma.

AIM: This study assesses a clinical potential of immediate early responsive gene X-1 (IEX-1), also named IER3, in the diagnosis of epithelial ovarian carcinoma using blood and salivary specimens. METHODS: Immediate early responsive gene X-1 was quantified in blood and saliva by real-time quantitative reverse transcription polymerase chain reaction in 26 cases of epithelial ovarian carcinoma, 37 cases of benign ovarian tumor and 55 cases of healthy women. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of IEX-1. RESULTS: Immediate early responsive gene X-1 was expressed in blood and saliva of the benign ovarian tumor group and the healthy women group, both at a level significantly higher than that of the ovarian carcinoma group (P < 0.017). There were no significant differences in IEX-1 expression in blood and saliva (P = 0.376 or 0.621, respectively) between the benign ovarian tumor and the healthy women group. Comparison of IEX-1 expression in blood between the ovarian carcinoma group and the benign ovarian tumor group or the healthy women group demonstrated the ROC-area under curves (AUC) of 0.947 or 0.929, respectively. In discriminating the ovarian carcinoma group from the benign ovarian tumor group, IEX-1 expression in blood demonstrated a sensitivity and specificity of 84.6% and 94.6%, respectively. Similarly, blood IEX-1 expression conferred a sensitivity of 84.6% and specificity of 90.9% in distinguishing the ovarian carcinoma group from the healthy women group. Moreover, salivary IEX-1 expression had ROC-AUC of 0.851 when compared between the ovarian carcinoma group and the benign ovarian tumor group or 0.896 when compared between the ovarian cancer group and the healthy women group. IEX-1 expression was able to discriminate the ovarian carcinoma group from the benign ovarian tumor group with a sensitivity and specificity of 65.4% and 94.6%, respectively, or the ovarian carcinoma from the healthy women with 92.3% sensitivity and 72.5% specificity. CONCLUSION: These results suggest the clinical potential of IEX-1 expression in blood and saliva as a sensitive and specific diagnosis for epithelial ovarian carcinoma.