miR‐200c overexpression inhibits the invasion and tumorigenicity of epithelial ovarian cancer cells by suppressing lncRNA HOTAIR in mice

Abstract

Epithelial ovarian cancer (EOC) is a common ovarian cancer in gynecological cancers today. It has been found that microRNAs and long‐chain noncoding RNA (lncRNA) regulate the gene transcriptional expression in cells. However, it is not well understood that the upstream and downstream regulatory molecules of lncRNA HOX antisense intergenic RNA (HOTAIR). The effects of miR‐200c overexpression on the invasion and nude mouse tumorigenicity, as well as lncRNA HOTAIR and snail expression of EOC SKOV3 cells, should be further explored. The expression of miR‐200c and lncRNA HOTAIR was detected by reverse transcription PCR (RT‐PCR) in EOC SKOV3 cells. The whole miR‐200c gene fragment was cloned into a lentiviral plasmid vector. The miR‐200c expression in transducted SKOV3 cells with reconstructed miR‐200c lentivirus was significantly higher than the negative control (P < .01). The lentivirus‐miR‐200c‐SKOV3 cells show that the invasion ability was significantly decreased compared with the negative control (P < .01). The nude mouse tumorigenicity was significantly decreased compared with that of the control group (P < .01). The snail protein expression in lentivirus‐miR‐200c‐SKOV3 xenograft tumor was significantly decreased compared with the negative control lentivirus‐SKOV3 group (P < .05). The miR‐200c overexpression significantly decreased the expressions of lncRNA HOTAIR and snail, but increased E‐cadherin expression in the lentivirus‐miR‐200c transducted SKOV3 cells of xenograft tumor, compared with the negative control (P < .05). The miR‐200c overexpression in SKOV3 cells with transducted lentivirus‐miR‐200c can inhibit lncRNA HOTAIR expression, decrease snail, increase E‐cadherin and significantly reduce the invasion and tumorigenicity of EOC SKOV3 cells. These results suggest that the miR‐200c and lncRNA HOTAIR could be effective therapeutic targets for human epithelial ovarian cancer treatment.

LncRNAs in Ovarian Cancer Progression, Metastasis, and Main Pathways: ceRNA and Alternative Mechanisms

“…The axis HOTAIR/miR-200c/SNAIL (or SNAI1, zinc finger transcription factor), involved in OvCa invasion, was demonstrated using transduced lentivirus-miR-200c, gain-or loss-of-function assays, EMT markers, and tumorigenicity of SKOV3 cells in xenograft tumor studies [118]. In recent work, it was shown that miR-138-5p could directly bind to HOTAIR and 3 -UTR of EZH2 (enhancer of zeste homolog 2, a histone-lysine N-methyltransferase) and SIRT1 (NAD-dependent deacetylase sirtuin 1), which was validated by the dual-luciferase reporter assay [119].…”

Long noncoding RNA PVT1 promotes tumor cell proliferation, invasion, migration and inhibits apoptosis in oral squamous cell carcinoma by regulating miR‑150‑5p/GLUT‑1

“…Abnormal expression of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs/miRs) has been demonstrated to be related to tumor formation and progression in various types of cancers (10)(11)(12). For example, lncRNA HOTAIR was found to be suppressed in ovarian cancer cells, which was found to inhibit the invasion and tumorigenicity by interacting with miR-200c in mice (11). lncRNA MIR4435-2HG was found to promote prostate cancer migration and invasion by upregulating TGF-β1 expression (10).…”

“…Long non-coding RNAs (lncRNAs) are a diverse class of RNA transcripts longer than 200 nucleotides that have limited protein coding capacity (7,8). lncRNAs have been found to participate in various biological processes in cancers such as cervical cancer, prostate carcinoma, epithelial ovarian cancer and breast cancer, including tumorigenesis, metastasis and chemotherapy resistance (9)(10)(11)(12). Recent evidence shows that lncRNAs play oncogenic or tumor-suppressor roles in OSCC (13)(14)(15).…”

The Role of Long Non-Coding RNAs (lncRNAs) in Female Oriented Cancers

“…The regulation of EMT-related genes and specific matrix metalloproteinases (MMPs) by HOTAIR is believed to be responsible for OC metastasis [ 117 , 118 ]. Moreover, the hyper-expression of HOTAIR is also co-related with specific miRNAs expressions [ 119 ]. For instance, HOTAIR upholds the OC stem cells stemness by upregulating a protein-coding gene TBX3 through the miR-206/TBX3 axis [ 120 ].…”