1. Roles of a TMPO-AS1/microRNA-200c/TMEFF2 ceRNA network in the malignant behaviors and 5-FU resistance of ovarian cancer cells.
- Author
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Li, Haoshan, Zhou, Yan, Cheng, Hailing, Tian, Jun, and Yang, Shaoqin
- Subjects
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CANCER cells , *OVARIAN cancer , *EPIDERMAL growth factor , *EPITHELIAL-mesenchymal transition , *FLUOROURACIL , *CANCER stem cells - Abstract
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. • LncRNA TMPO-AS1 is overexpressed in OC, which is related to drug resistance. • Si-TMPO-AS1 or miR-200c mimic inhibits OC cell metastasis and chemoresistance. • LncRNA TMPO-AS1 regulates the miR-200c/TMEFF2 axis by functioning as a ceRNA. • TMPO-AS1 upregulates TMEFF2 to activate the Akt/PI3K pathway via sponging miR-200c. • The main results suggest TMPO-AS1 might be a potential target in OC treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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