Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1140680 (ovarian cancer)
 28,141 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Competing endogenous RNA (ceRNA) networks consisted of long non-coding RNA (lncRNA), microRNA (miRNA) and mRNAs have aroused great interests recently. The current study aims to probe the mechanisms of lncRNA TMPO-AS1 in ovarian cancer (OC) development. A 5-fluorouracil (5-FU)-resistant subline of OC SKOV3 cells was developed, and differentially expressed lncRNAs in OC tissues and SKOV3 cells were analyzed. The miRNAs, genes and signaling pathways interacted with TMPO-AS1 were predicted and validated. TMPO-AS1 and the validated miRNA were inhibited to analyze their roles in malignant behaviors and 5-FU resistance of OC cells. In vivo studies were performed by inducing xenograft tumors in nude mice. Consequently, TMPO-AS1 was highly expressed in OC tissues and SKOV3 cells. TMPO-AS1 regulated transmembrane protein with epidermal growth factor and two follistatin motifs 2 (TMEFF2) through sponging miR-200c in OC cells, during which the PI3K/Akt signaling pathway was activated. Silenced TMPO-AS1 and over-expressed miR-200c inhibited epithelial-mesenchymal transition (EMT), invasion, migration and 5-FU resistance of OC cells. This study demonstrated that silencing of TMPO-AS1 might attenuate OC progression through inhibiting the invasion, metastasis and drug resistance of OC cells via the miR-200c/TMEFF2 network and the disruption of the PI3K/Akt signaling pathway.
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PMID:Roles of a TMPO-AS1/microRNA-200c/TMEFF2 ceRNA network in the malignant behaviors and 5-FU resistance of ovarian cancer cells. 3249 21

Ovarian cancer remains the sixth most frequently occurring cancer in women worldwide. Long noncoding RNAs (lncRNAs) are capable of regulating gene expression, and thus, participating in a wide range of biological functions and disease processes including cancer development. Our work suggests that lncRNA TMPO antisense RNA 1 (TMPO-AS1) represents an oncogenic lncRNA in ovarian cancer and presents a novel mechanism involving transcription factor E2F transcription factor 6 (E2F6) and lipocalin-2 (LCN2). We identified upregulated lncRNA TMPO-AS1 in ovarian cancer tissues and cells. siRNA-mediated silencing of lncRNA TMPO-AS1 restrained the aggressiveness of ovarian cancer cells and their pro-angiogenic ability, and reduced the expression of LCN2. LncRNA TMPO-AS1 was found to interact with E2F6, a transcriptional repressor that could bind to the promoter region of LCN2 gene. In addition, silencing of E2F6 or overexpression of LCN2 restored the aggressiveness of ovarian cancer cells and their pro-angiogenic ability following siRNA-mediated silencing of lncRNA TMPO-AS1. Taken together, we demonstrated lncRNA TMPO-AS1 could potentially promote LCN2 transcriptional activity by binding to transcription factor E2F6, and thus, stimulated the progression of ovarian cancer. These findings underscore a possible alternative therapeutic strategy for ovarian cancer treatment.
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PMID:LncRNA TMPO-AS1 promotes LCN2 transcriptional activity and exerts oncogenic functions in ovarian cancer. 3269 67