Anti-TBPL1 monoclonal antibody Made to order

Recent advances in the understanding of microRNA have rendered microRNAs (miRNAs) a compelling novel class of biomarker in cancer biology. However, the specific function of miRNA-18a (miR-18a) in colorectal cancer (CRC) remains unclear. In the present study, the role of miR-18a in the carcinogenesis of CRC was investigated. miR-18a expression was assessed in CRC specimens and cell lines using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The targets of miR-18a were predicted using bioinformatics tools. Luciferase reporter assays were used to confirm the functional association between miR-18a and its target genes. The effect of miR-18a on cell proliferation, invasion and migration was confirmed in vitro by a methylthiazol tetrazolium assay, cell invasion assay, and wound healing assay. Gene and protein expression was examined using RT-qPCR and western blotting, respectively. It was demonstrated that the expression of miR-18a in CRC tissues and cell lines was markedly lower than in normal control tissues and cells, respectively. In addition, miR-18a inhibited cell proliferation, invasion and migration in CRC cells. Moreover, TATA box-binding protein-like protein 1 (TBPL1) was identified as a potential target gene of miR-18a in the bioinformatics analysis and luciferase reporter assays, and miR-18a directly inhibited TBPL1 expression by targeting its 3'-untranslated region. Furthermore, TBPL1 was downregulated and inversely correlated with miR-18a expression in tissues. These findings demonstrate that miR-18a exhibits a protective role in CRC via inhibiting proliferation, invasion and migration of CRC cells by directly targeting the TBPL1 gene.

Purpose: Pulmonary carcinoid tumors account for up to 5% of all lung malignancies in adults, comprise 30% of all carcinoid malignancies, and are defined histologically as typical carcinoid (TC) and atypical carcinoid (AC) tumors. The role of specific genomic alterations in the pathogenesis of pulmonary carcinoid tumors remains poorly understood. We sought to identify genomic alterations and pathways that are deregulated in these tumors to find novel therapeutic targets for pulmonary carcinoid tumors. Experimental Design: We performed integrated genomic analysis of carcinoid tumors comprising whole genome and exome sequencing, mRNA expression profiling and SNP genotyping of specimens from normal lung, TC and AC, and small cell lung carcinoma (SCLC) to fully represent the lung neuroendocrine tumor spectrum. Results: Analysis of sequencing data found recurrent mutations in cancer genes including ATP1A2, CNNM1, MACF1, RAB38, NF1, RAD51C, TAF1L, EPHB2, POLR3B, and AGFG1. The mutated genes are involved in biological processes including cellular metabolism, cell division cycle, cell death, apoptosis, and immune regulation. The top most significantly mutated genes were TMEM41B, DEFB127, WDYHV1, and TBPL1. Pathway analysis of significantly mutated and cancer driver genes implicated MAPK/ERK and amyloid beta precursor protein (APP) pathways whereas analysis of CNV and gene expression data suggested deregulation of the NF-kappa B and MAPK/ERK pathways. The mutation signature was predominantly C>T and T>C transitions with a minor contribution of T>G transversions. Conclusions: This study identified mutated genes affecting cancer relevant pathways and biological processes that could provide opportunities for developing targeted therapies for pulmonary carcinoid tumors. (C) 2018 AACR.