Dataset Information

Multi-omics profiling reveals key signaling pathways in ovarian cancer controlled by STAT3.

ABSTRACT: Inhibiting STAT3 signaling reduces tumor progression, metastasis and chemoresistance, however the precise molecular mechanism has not been fully delineated in ovarian cancer. METHODS:In this study, we generated STAT3 knockout (KO) ovarian cancer cell lines. Effects of STAT3 KO on cell proliferation, migration and spheroid formation were assessed in vitro and effects on in vivo tumor growth were tested using several tumor xenograft models. We used multi-omic genome-wide profiling to identify multi-level (Bru-Seq, RNA-Seq, and MS Proteomic) expression signatures of STAT3 KO ovarian cancer cells. RESULTS:We observed that deletion of STAT3 blocked cell proliferation and migration in vitro and suppressed tumor growth in mice. Deletion of STAT3 transcriptionally suppressed key genes involved in EMT, cell cycle progression, E2F signaling, and altered stemness markers. Notably, KO of STAT3 resulted in modulation of the expression of other STAT family members. CONCLUSION:Our study presents a rich, multi-faceted summary of the molecular mechanisms impacted by STAT3 deletion and provides new insight for STAT3's potential as a therapeutic target in ovarian cancer.

SUBMITTER: Lu T

PROVIDER: S-EPMC6735387 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Multi-omics profiling reveals key signaling pathways in ovarian cancer controlled by STAT3.

Lu Tiangong T Bankhead Armand A Ljungman Mats M Neamati Nouri N

Theranostics 20190728 19

Inhibiting STAT3 signaling reduces tumor progression, metastasis and chemoresistance, however the precise molecular mechanism has not been fully delineated in ovarian cancer.<h4>Methods</h4>In this study, we generated <i>STAT3</i> knockout (KO) ovarian cancer cell lines. Effects of <i>STAT3</i> KO on cell proliferation, migration and spheroid formation were assessed <i>in vitro</i> and effects on <i>in vivo</i> tumor growth were tested using several tumor xenograft models. We used multi-omic gen ...[more]

PMID: 31534498

Similar Datasets

Project description:BACKGROUND:Ovarian follicle development plays an important role in determination of poultry egg production. The follicles at the various developmental stages possess their own distinct molecular genetic characteristics and have different biological roles in chicken ovary development and function. In the each stage, several genes of follicle-specific expression and biological pathways are involved in the vary-sized follicular development and physiological events. Identification of the pivotal genes and signaling pathways that control the follicular development is helpful for understanding their exact regulatory functions and molecular mechanisms underlying egg-laying traits of laying hens. RESULTS:The comparative mRNA transcriptomic analysis of ovarian follicles at three key developmental stages including slow growing white follicles (GWF), small yellow follicles (SYF) of recruitment into the hierarchy, and differentiated large yellow follicles (LYF), was accomplished in the layers with lower and higher egg production. Totally, 137, 447, and 229 of up-regulated differentially expressed genes (DEGs), and 99, 97, and 157 of down-regulated DEGs in the GWF, SYF and LYF follicles, including VIPR1, VIPR2, ADRB2, and HSD17B1 were identified, respectively. Moreover, NDUFAB1 and GABRA1 genes, two most promising candidates potentially associated with egg-laying performance were screened out from the 13 co-expressed DEGs in the GWF, SYF and LYF samples. We further investigated the biological effects of NDUFAB1 and GABRA1 on ovarian follicular development and found that NDUFAB1 promotes follicle development by stimulating granulosa cell (GC) proliferation and decreasing cell apoptosis, increases the expression of CCND1 and BCL-2 but attenuates the expression of caspase-3, and facilitates steroidogenesis by enhancing the expression of STAR and CYP11A1. In contrast, GABRA1 inhibits GC proliferation and stimulates cell apoptosis, decreases the expression of CCND1, BCL-2, STAR, and CYP11A1 but elevates the expression of caspase-3. Furthermore, the three crucial signaling pathways such as PPAR signaling pathway, cAMP signaling pathway and neuroactive ligand-receptor interaction were significantly enriched, which may play essential roles in ovarian follicle growth, differentiation, follicle selection, and maturation. CONCLUSIONS:The current study provided new molecular data for insight into the regulatory mechanism underlying ovarian follicle development associated with egg production in chicken.

Dataset Information

Multi-omics profiling reveals key signaling pathways in ovarian cancer controlled by STAT3.

Publications

Multi-omics profiling reveals key signaling pathways in ovarian cancer controlled by STAT3.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure