| Ovarian carcinoma is characterized as hardly discoverable, high metastasis, poor prognosis etc. It is one of the most common malignancy among female population with highst mortality rate comparing to other gynecological malignancies, which has the incidence of about 22.9% and increasing at the rate of 1% annually. amony gynecological malignancies, the most common one is called epithelial ovarian cancer(EOC), which account for 85-90% cases of the total ovarian cancer. Ovarian carcinoma may happen at any age,but 40 and 70 years old wemen take the higher risk. the 5-year survival rate are only about 30%, even with the best medical treament currently. Because there are no pathological signs at the early stage of ovarian carcinoma, patients only went to hospital when the pain from waist and abdominal occurs or the digestive tract symptom was detectable. With those reasons, 2/3 of the patients are diagnosed at an the advanced stage of the illness, and more than of 70% of them has tumor transferred or metastasis of pelvic lymph node. For patients with advanced ovarian cancer, chemotherapy is the main treatment.Such chemotherapy plays an important role in the comprehensive treatment of ovarian cancer. Presently, the Paclitaxel and platinum-containing chemotherapy is still the main scheme for dealing with the advanced ovarian carcinoma. Among them, cisplatin as first-line chemotherapy drugs are widely used in many advanced tumors. But due to various reasons, the primary and compensatory drug resistance occurs frequently.the tumor cells of primary or secondary drug resistance is an important factor affecting the effect of chemotherapy, and is the main cause of tumor recurrence. Platinum resistance comes from various mechanisms, including: internal and external environment changes, reduce drug intake by tumor cells, enhanced cellular detoxification, enhancement of DNA damage repair capacity, blockage of apoptosis pathway and so on. Although platinum-based chemotherapy has made new progress, the 5-year survival rate did not significantly increase, which clearly cisplatin resistance mechanisms to find effective resistance reversal agents to improve ovarian cancer chemosensitivity and adjust the treatment plan is of great significance. To improve the survival rate of ovarian carcinoma, the seeking for drug-resistance mechanism seems essential, which have significant meanings in improving chemosensitivity, modulating therapeutic scheme and reversing drug resistance.At the same time, the importance of non-coding RNA in disease regulation has gradually been revealed. Non-coding RNA have been proved to be involved in many complex diseases, such as autoimmune diseases sn RNAs participate the occurance of many autoimmune diseases like systemic lupus erythematosusas, sno RNAs are associated with scleroderma and so on. In addition, non-coding RNAs were proved to have the function of tumorigenesis blockage or correlate with cell abnormalities and cancer formation. For example, mi R-15 and mi R-16, as tumor suppressing genes, plays an important role in human chronic lymphocytic leukemia process. From the family of non-coding RNAs, one of the important member called long non-coding RNAs(Lnc RNA) were identificed as the regulator of various neoplastic diseases including gastric cancer, liver cancer, lung cancer and etc. the changes of Lnc RNA expression levels or even spatial structure change of them would cause significant proteins expression alteration downstream, which is thought to be one of the basic mechanism for cancer development. For example, HOTAIR could mediated the chromatin remodeling and cancer metastasis. It is believed that the interaction between HOTAIR and PRC2(polycomb repressive complex 2) accelerates cancer metastasis by causing changes in chromatin methylation status. And more recent studies have found that Lnc RNAs may be tightly associated with the development of ovarian cancer. Therefore, the analysis and studies for finding the functional mechanisms of Lnc RNAs in mediating the cisplatin resistance would be significantly necessary. Within this research, using ovarian cancer cell line called A2780(cisplatin-sensitive) and CP70(cisplatin resistance) as the research object, introducing Lnc RNA/m RNA gene chip analysis as well as real-time quantitative PCR and immunocytochemistry as the experimental methods, we intend to interpret the total change between cisplatin resistance tumor cells and cisplatin sensitive cells in Lnc RNA and m RNA genes expression level, and analyze the relationship between Lnc RNA expression changes and associated m RNAs regulation, which may probably leads to cisplatin resistance. The experiement revealed that the Lnc RNA candidate U2 can significantly promote cisplatin-resistant and the formation of the resistant mediated by U2 was coralated with the function of U2 regulation on Bax/Bcl-2 expression level. The study will provide strong experimental evidence for seeking into cisplatin-resistant related Lnc RNAs, and build the foundational contributes for further explorations on the mechanism of cisplatin resistance in Lnc RNAs level. |
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