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Our recent study has shown that TRIM36, a member of tripartite motif-containing (TRIM) family proteins and tumor suppressor and β-catenin may serve as a prognostic biomarker for esophageal squamous cell carcinoma (ESCC). Here, we sought to examine functional roles of TRIM36 and β-catenin in ESCC cells. TRIM36 was overexpressed or silenced by lentivirus transduction. Cell proliferation was examined by Cell Counting Kit (CCK)-8 assay, while cell cycle distribution and cell apoptosis was assessed via flow cytometry analysis. Xenograft mouse model was applied for in vivo analysis. Overexpression of TRIM36 inhibited cell proliferation in human ESCC cells, and silencing of TRIM36 led to opposite effects. We also found that ectopic expression of TRIM36 enhanced the ratio of G0/G1 phase cells and induced apoptosis in ESCC cells. Our data further revealed that TRIM36 stimulated the ubiquitination of β-catenin, and in turn, its inactivation. Finally, we confirmed these in vitro results in a xenograft mouse model and clinical specimens post-operatively obtained from patients of ESCC. In summary, these data support that TRIM36 can effectively inhibit tumorigenesis of ESCC by repressing Wnt/β-catenin signaling pathway, which suggest that selectively repressing this signaling pathway in ESCC may lead to development of a novel therapeutic approach for controlling this disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Liver receptor homolog-1 (LRH-1) is highly observed in tissues with secretory function, such as the ovaries, suggesting that LRH-1 may play an essential role in the ovarian endocrine. In particular, ovarian granulosa cells (GCs) are the functional cells that produce steroid hormones. The fate of GCs directly affects follicular development or atresia. These effects were lost in granulosa-specific LRH-1-knockout mice, showing that LRH-1 is a central modulator of ovarian function. However, the underlying mechanism LRH-1 in the bovine ovaries remains unclear. We aimed to detect the effect of LRH-1 on steroid hormones in bovine GCs and explore the potential relationship between LRH-1 and the fate of GCs. The results show that LRH-1 was specifically highly expressed in GCs of atretic follicles. Mechanistically, LRH-1 induced the apoptosis of bovine GCs by the progestogen receptor signaling pathway. While this finding provided new ideas for the study of follicular atresia, it also provided a theoretical basis for the clinical diagnosis and treatment for infertility in cow. The purpose of the present investigation was to assess the function of LRH-1 on GCs and the mechanisms involved. Here, LRH- was highly expressed in the bovine GCs of atretic follicles. Treatment with 50 μM of LRH-1 agonist (DLPC) significantly induced the expression of LRH-1 (p < 0.05). In particular, LRH-1 activation blocked the progestogen receptor signaling pathway via downregulating progesterone production and progestogen receptor levels (p < 0.05), but had no effect on 17 beta-estradiol synthesis. Meanwhile, LRH-1 activation promoted the apoptosis of GCs and increased the activity of caspase 3 (p < 0.05). Importantly, upregulating the progestogen receptor signaling pathway with progestogen could attenuate the LRH-1-induced proapoptotic effect. Moreover, treatment with progestogen decreased the activity of the proapoptotic gene caspase 3 and increased the expression of antiapoptotic gene Bcl2 in LRH-1 activated GCs (p < 0.05). Taken together, these results demonstrate that LRH-1 might be dependent on the progestogen receptor signaling pathway to modulate bovine follicular atresia. [ABSTRACT FROM AUTHOR]

The transcription factor signal transducer and activator of transcription 3 (STAT3) contributes to cell proliferation, apoptosis and motility in human cancer cells. We aim to elucidate the function of STAT3 in esophageal carcinogenesis process and molecular mechanisms. We showed that hyperactivated STAT3 in esophageal carcinogenesis tissues correlated with the overexpression of octamer transcription factor-1 (Oct-1). High STAT3 phosphorylation correlated with shorter survival compared with low STAT3 phosphorylation. STAT3 and Oct-1 expression levels affected the proliferation and colony formation of Eca-109 esophageal squamous cell carcinoma cells by altering Erk and Akt activation. Nevertheless, STAT3 regulated the migration and invasion of esophageal squamous cell carcinoma cells independent of Oct-1. In conjunction with Oct-1, STAT3 inhibited apoptosis in esophageal squamous cell carcinoma cells. Constitutively activated STAT3 in normal human esophageal epithelium cells (HET-1A) elevated Oct-1 expression,and promoted proliferation and decreased apoptosis. STAT3 activated HET-1A cells to form tumors in vivo, suggesting that overactivated STAT3 is sufficient for carcinogenesis. We further confirmed the colocalization of STAT3 and Oct-1 in the nucleus and found that STAT3 regulates the transcription and expression of Oct-1 by directly targeting its promoter. Activated STAT3 also upregulated many genes associated with Oct-1. Together, our results indicate that STAT3 plays a crucial role in esophageal carcinogenesis by regulating the cell proliferation and apoptosis in conjunction with Oct-1. [ABSTRACT FROM AUTHOR]