Dengyu Chen

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.

Attenuated Salmonella typhimurium L forms combined with lentivirus shRNA-HOTAIR effectively inhibit tumor growth and metastasis in murine epithelial ovarian cancer

Epithelial ovarian cancer (EOC) is a common gynecological malignant tumor, with a high mortality rate. HOX antisense intergenic RNA (HOTAIR) in lncRNAs is involved in various tumor epithelial-mesenchymal transition (EMT) processes. For seeking better treatment strategies, we studied the effects of attenuated Salmonella typhimurium (ST) L forms combined with lentivirus shRNA-HOTAIR on in vivo tumorigenicity and metastasis of murine EOC cells, and the related anti-tumor mechanisms. Attenuated ST VNP20009 was induced into bacterial L forms by using ceftriaxone. ST L forms were appeared red in Gram staining. Attenuated ST L forms can inhibit the invasion ability of EOC cells in vitro. TUNEL assays showed that attenuated ST L forms combined with lentivirus shHOTAIR can induce more apoptosis of ID8 cells in murine ovarian tumors, compared to the negative control group and only ST or bacterial L forms therapy group. Meanwhile, attenuated ST L forms combined with lentivirus shHOTAIR more effectively inhibited tumor growth and lung metastasis in murine ovarian tumors. The tumorigenicity-related proteins of xenograft tumors detected by immunohistochemistry and qRT-PCR assays showed that attenuated ST L forms combined with lentivirus shHOTAIR can more effectively decrease the protein and mRNA expressions which promote tumor growth and metastasis, such as TGF-β1, ZEB1 and Vimentin. This study confirmed that attenuated ST L forms combined with lentivirus shHOTAIR can more effectively suppress tumor growth and lung metastasis in murine ovarian tumors. Attenuated ST L forms combined with lentivirus shHOTAIR may serve as a better novel biological strategy for bacterial-mediated tumor therapy in EOC.