MiR-378 as a biomarker for response to anti-angiogenic treatment in ovarian cancer
GYNECOLOGIC ONCOLOGY
Authors: Chan, John K; Kiet, Tuyen K.; Blansit, Kevin; Ramasubbaiah, Rashmi; Hilton, Joan F.; Kapp, Daniel S.; Matei, Daniela
Abstract
Objective. To determine the role of miR-378 as a biomarker for anti-angiogenic therapy response in ovarian cancer. Methods. Expression of miR-378 was analyzed in ovarian cancer cell lines and human tumors vs. normal ovarian epithelial cells by qRT-PCR. After miR-378 transfection in SKOV3 cells, dysregulated genes were identified using microarray. Data from The Cancer Genome Atlas (TCGA) was utilized to correlate miR-378 expression with progression-free survival (PFS) among patients treated with anti-angiogenic therapy by using Kaplan-Meier and Cox proportional hazards. Results. MiR-378 was overexpressed in ovarian cancer cells and tumors vs. normal ovarian epithelial cells. Overexpressing miR-378 in ovarian cancer cells altered expression of genes associated with angiogenesis (ALCAM, EHD1, ELK3, TLN1), apoptosis (RPN2, HIPK3), and cell cycle regulation (SWAP-70, LSM14A, RDX). In the TCGA dataset, low vs. high miR-378 expression was associated with longer PFS in a subset of patients with recurrent ovarian cancer treated with bevacizumab (9.2 vs. 4.2 months; p = 0.04). On multivariate analysis, miR-378 expression was an independent predictor for PFS after anti-angiogenic treatment (HR = 2.04, 95% Cl: 1.12-3.72; p = 0.02). Furthermore, expression levels of two miR-378 targets (ALCAM and EHD1) were associated with PFS in this subgroup of patients who received anti-angiogenic therapy (9.4 vs. 4.2 months, p = 0.04 for high vs. low ALCAM; 7.9 vs. 23 months, p < 0.01 for low vs. high EHD1). Conclusions. Our data suggest that miR-378 is overexpressed in ovarian cancer cells and tumors vs. normal ovarian epithelial cells. MiR-378 and its downstream targets may serve as markers for response teo anti-angiogenic therapy. (C) 2014 Elsevier Inc. All rights reserved.
Molecular characterization and expression of the teleost cytosolic DNA sensor genes cGAS, LSm14A, DHX9, and DHX36 in Japanese medaka, Oryzias latipes
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
Authors: Murakami, Shiori; Morimoto, Natsuki; Kono, Tomoya; Sakai, Masahiro; Hikima, Jun-ichi
Abstract
Numerous cytosolic DNA sensors (CDSs), which are very important for recognizing cytosolic dsDNA derived from intracellular viruses and bacteria, exist in mammals. However, teleost CDSs are poorly understood. In this study, four CDSs, including the cyclic GMP-AMP synthase (cGAS), Sm-like protein 14 homolog A (LSm14A), DEAH-box helicase (DHX) 9, and DHX36 genes were identified in Japanese medaka, Oryzias latipes, and their expression patterns were elucidated. The expression of these genes was upregulated in the intestines and kidney of CpG-ODN-stimulated medaka. The cGAS and LSm14A genes were significantly induced in the intestines, kidney, and spleen of formalin-killed Edwardsiella tarda-treated medaka; the DHX9 and DHX36 genes were not. cGAS gene expression was induced only in the intestines of live E. tarda-treated medaka. These results suggest that the transcription of four CDS genes of medaka responds to dsDNA stimulation, and cGAS is probably more important for the immune response against E. tarda infection.