| 【Objective】Epithelial ovarian cancer is characterised by a high incidence,difficulty in early diagnosis,and a high incidence of recurrence and drug resistance,making it the fifth leading killer of women’s tumours.The first-line treatment for ovarian cancer is initial cytoreductive surgery combined with platinum-based chemotherapy.There are currently three PARP inhibitors that have been approved by FDA for use in ovarian cancer.They can be used as a backline treatment for patients with recurrent BRCA-mutated ovarian cancer or as maintenance therapy for ovarian cancer.And Niraparib can be used with or without BRCA mutations.However,there has been less discussion on the resistance and mechanisms of these targeted agents.LRRC15,a member of the LRR superfamily,is a type I transmembrane protein consisting of 15 leucine-rich repeat sequences.Previous studies have shown that LRRC15 is highly expressed in a variety of tumour tissues and lowly expressed in corresponding normal tissues.This differential expression may be involved in promoting the progression and metastasis of breast cancer and osteosarcoma,etc.The impact of LRRC15 in ovarian cancer is currently unclear.This study will investigate the expression of LRRC15 in ovarian cancer and the effect of LRRC15 on ovarian cancer cells and ovarian cancer PARP inhibitor resistant cells.【Methods】The expression of LRRC15 in different tissues was obtained by mining the TCGA database and the GTEx database for ovarian serous cystadenocarcinoma,and then the results were enriched and analyzed,and the relationship between LRRC15 and the prognosis of ovarian cancer patients was also obtained by KMplot and TCGA database.Western blot and RT-q PCR were used to validate the data.The cells were transfected with lentivirus to knock down or overexpress LRRC15,and Olaparib-resistant strains of ovarian cancer cells were established to mimic the resistance of ovarian cancer patients to PARP inhibitors.The effect of LRRC15 on ovarian cancer cells was verified using scratch assays,clone formation assays and transwell invasion assays.The miRNAs associated with LRRC15 were screened against the database and validated.Finally,in situ tumour formation in nude mouse ovaries was used to observe the role of LRRC15 in ovarian cancer and ovarian carcinoma Olaparib-resistant cells.【Results】(1)LRRC15 was differentially expressed,it was highly expressed in ovarian cancer,and LRRC15 expression is correlated with prognosis.(2)LRRC15 may be highly expressed in high-grade ovarian serous cystadenocarcinoma,but not in clear cell carcinoma.(3)LRRC15high expression promoted invasion and metastasis of ovarian cancer cells.(4)CAOV3-OR and OVCAR8-OR were established as two strains of ovarian cancer Olaparib-resistant cells.(5)Lowering LRRC15 increased the sensitivity of ovarian cancer cells to Olaparib.(6)miR-146a-5p may be involved in regulating LRRC15. |
PDF Full Text Request