The Difference Of Expression Of LncRNA In Human Endometrial Cancer Cell And The Activation Of Endoplasmic Stress Pathway Induced By Medroxyoprogesterone Acetate

Objective:To determine the effect of Medroxyprogesterone Acetate(MPA)on apoptosis and cell cycle of endometrial cancer cell in vitro,and to find a factor、lnc RNA or pathway which may mediate the effect of MPA on PR~+endometrial cancer cell,predict the potential target for treatment of PR~-endometrial cancer.Method:We analysed the pathological information of the specimens obtained from endometrial cancer patients who underwent hysterectomy and determine the relativity between expression of progesterone receptor(PR)and the grade or stage of this disease.Flow cytometry was applied to detect the different effect of MPA on Ishikawa(endometrial cancer cell,PR~+)and KLE(endometrial cancer cell,PR~-).Then we used a gene chip to detect the different expression of LncRNA and m RNA in Ishikawa after MPA treatment.q PCR was employed to validate the results of chip.Co-expression analysis、GO function enrichment analysis and KEGG pathway analysis help to predict the biological function influenced by MPA in cell.We screened some factors and lnc RNA which may involed in regulating cell cycle and apoptosis,then validate their expression level in Ishikawa and KLE respectively.Result:1.The specimens that express PR tend to a greater situation in the myometrial invasion;The specimens with higher PR expression tend to a higher pathological grade。2.MPA treatment on Ishikawa will significantly increased the level of apoptotic cell and cell in G1/S phase,but it doesn’t show obvious action in KLE;3.Chip information shows that 358 m RNA and 292 LncRNA upregulated and 778m RNA and 655 LncRNA downregualated after MPA treatment in Ishikawa.q PCR result supports the chip data.GO、KEGG and co-expression analysis predict that endoplasmic reticulum stress(ERS)may be activated by the MPA.Chip data showed that The ESR-related apoptosis factors CHOP and ERS-related factor HERPUD were upregulated in Ishikawa-MPA group.Correlation analysis showed that lnc-CETP-3 co-expressed both with CHOP and with HERPUD1.We predict lnc-CETP-3 may involve in regulating cell cycle、apoptosis and cancer pathway.4.In Ishikawa,lnc-CETP-3 is significantly upregulated in MPA group,the expression of CHOP and HERPUD1 are significantly increased both in m RNA level and in protein level after MPA treatment.In KLE,there is no statistic difference in lnc-CETP-3 level between two group;the expression of CHOP doesn’t Show statistical difference neither in m RNA level or in protein level;the expression of HERPUD1also doesn’t show difference in m RNA level,but shows a slight increase in protein level after MPA treatment.Conclusion:MPA activates endoplasmic reticulum stress in endometrial cancer cell by acting on PR.the ERS-related factor CHOP may mediate the process of promoting apoptosis in PR~+endometrial cancer cell by MPA.lnc-CETP-3 may involve in process above.