| [Background] Ovarian cancer, as one of three major gynecologic malignant tumors,remains the first cause of death worldwide. The incidence gradually rose year by year.However, the tumorigenesis and progress mechanism are still unknown. Ovarian cancerincludes a wide range of subtypes, among which, there are85-90%epithelial ovariancancer. It is thought in origin to be related with those undifferentiated cells in the cambiumlayer of ovarian surface. Once genetic mutation has occurred, or oncogenes exist, it isprone to form malignant tumors. As the result, from the perspective of molecular biology,it is critical to do some researches to understand the machenisms of epithelial ovariancancer. There is accumulating evidence and efforts indicating a vast hidden butsurprisingly prominent layer of regulatory macro ncRNAs, named long non-coding RNAs,accounting for4-9%of human genome. LncRNAs, more than200nucleotides in length,constitutes the majority of the genomic programming and be implicated in the regulation ofgene expression in many types of ways, including epigenetic, transcriptional orpost-transcriptional regulation and so forth, sequentially inducing development of cancersand other diseases. Finding specific long non-coding RNA of epithelial ovarian cancer isone of most important ways to understand the machenism. In2003, Rangel et al. havedemonstrated that a new transcript, named human ovarian cancer-specific transcript2(HOST2) specifcally express in all four major clinicopathologic subtypes of ovarianmalignancy. However, their research did not mention the functions and regulation ofHOST2in epithelial ovarian cancer, and until now, there is barely any literation about thisarea.[Objects]Verify the specific expression of HOST2in epithelial ovarian cancer; Testwhether HOST2, along with its regulatory molecule, contribute to biological functions;Explore the mechanism of HOST2and its regulatory molecule in epithelial ovarian cancerthrough bioinformatics, protein spectrum and other technologies, in order toprovidetheoretical foundation and experimental data, and finially may identify new earlydiagnosis and therapy targets of epithelial ovarian cancer.[Methods] Bioinformatics methods provide predictions about the regulatory molecules andtheir possible signal pathways of HOST2. OVCAR-3cell line is used to be cytologicalsubjects, and clinical tissue samples of epithelial ovarian cancer (n=50) and epithelialovarian tumors (n=50) are histological subjects. mRNA expression was evaluated by quantitative real-time polymerase chain reaction, protein expression by Western blot, andlocation detection by in situ hybridization, immunofluorescence or immunologicalhistological chemistry. Changing endogenous level of HOST2and/or its related genes byliposome transfection, and then test the effects on biological behaviours of tumor cells invitro and in vivo. Detect possible related microRNAs of HOST2through reporter geneassays.[Results] HOST2specifically high expresses in human epithelial ovarian cancer, andparticipates in migration, invasion and proliferation of tumor cells. HOST2sequenceshares a541nt similar sequence with C1orf186transcript. HOST2was illustrated tofunction as a sponge to bind with miR-1266, sequentially inhibiting combination betweenmiR-1266and C1orf186transcript, thus maintaining C1orf186expression. C1orf186alsospecifically high expresses in epithelial ovarian cancer both at mRNA and protein levles.The rate of C1orf186＋cells if closely related to the degree of malignancy, and thispopulation has a strone tumorigenicity. The expression level of phosphorylated STAT3inC1orf186＋cells is far higher than that in C1orf186－cells.C1orf186protein was shown toactivate the STAT3signaling pathway through an interaction with JAK2, therebymaintaining C1orf186＋cells survival.[Conclusions] In the study, a novel HOST2-related C1orf186-JAK2-STAT3pathway isdemonstrated to maintain C1orf186＋population. HOST2and C1orf186expressions act ascancer-specific events that may be contributed to diagnostic and therapeutic approaches forepithelial ovarian cancer patients. |
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