Anti-PTTG1 (aa 148-160) polyclonal antibody

Background: MicroRNAs (miRNAs) can act as either oncogenes or tumor suppressor genes under different conditions and thus can play a significant role in cancer development. We investigated miR-655 expression in a cohort of esophageal squamous cell carcinoma (ESCC) to assess the impact of this miRNA on ESCC cell invasion and metastasis. Methods: A qRT-PCR assay was used to quantify miR-655 expression levels in 34 paired ESCC samples and adjacent non-tumor tissues. Wound healing and transwell assays were used to evaluate the effects of miR-655 expression on the invasiveness of ESCC cells. Luciferase reporter and western blot assays were used to determine whether the mRNA encoding pituitary tumor-transforming gene-1 (PTTG1) is a major target of miR-655. Results: The expression level of miR-655 in ESCC tissues was found to be lower than in adjacent non-tumor tissues (P < 0.05). This relatively low expression level was significantly associated with the occurrence of lymph node metastases (P < 0.05). Migration rates were significantly lower for two ESCC-derived cell lines (EC9706 and KYSE150) transfected with miR-429 mimics (P < 0.05). Subsequent western blot and luciferase reporter assays demonstrated that miR-655 could bind to putative binding sites within the PTTG1 mRNA 3'-untranslated region (3'-UTR) and thus reduce the expression. Conclusions: miR-655 is expressed at low levels in primary ESCC tissues, and up-regulation of miR-655 inhibits ESCC cell invasiveness by targeting PTTG1. Our findings suggest that PTTG1 may act as a major target of miR-655. This study improves our understanding of the mechanisms underlying ESCC pathogenesis and may promote the development of novel targeted therapies.

Somatic driver mechanisms of pituitary adenoma pathogenesis have remained incompletely characterized; apart from mutations in the stimulatory G alpha protein (G alpha(s) encoded by GNAS) causing activated cAMP synthesis, pathogenic variants are rarely found in growth hormone-secreting pituitary tumors (somatotropinomas). The purpose of the current work was to clarify how genetic and epigenetic alterations contribute to the development of somatotropinomas by conducting an integrated copy number alteration, whole-genome and bisulfite sequencing, and transcriptome analysis of 21 tumors. Somatic mutation burden was low, but somatotropinomas formed two subtypes associated with distinct aneuploidy rates and unique transcription profiles. Tumors with recurrent chromosome aneuploidy (CA) were GNAS mutation negative (Gsp(-)). The chromosome stable (CS) -group contained Gsp(+) somatotropinomas and two totally aneuploidy-free Gsp(-) tumors. Genes related to the mitotic G(1)-S-checkpoint transition were differentially expressed in CA- and CS-tumors, indicating difference in mitotic progression. Also, pituitary tumor transforming gene 1 (PTTG1), a regulator of sister chromatid segregation, showed abundant expression in CA-tumors. Moreover, somatotropinomas displayed distinct Gsp genotypespecific methylation profiles and expression quantitative methylation (eQTM) analysis revealed that inhibitory G alpha (G alpha(i)) signaling is activated in Gsp(+) tumors. These findings suggest that aneuploidy through modulated driver pathways may be a causative mechanism for tumorigenesis in Gsp(-) somatotropinomas, whereas Gsp(+) tumors with constitutively activated cAMP synthesis seem to be characterized by DNA methylation activated G alpha(i) signaling.