Study on the Role of Low Expression SLC1A4 in Cisplatin Resistance in Ovarian Cancer
- VernacularTitle:低表达SLC1A4在卵巢癌顺铂耐药中的作用研究
- Author:
Landi SU
1
;
Jianming PENG
1
;
Yixiao BAO
1
;
Guozheng SUN
1
;
Fanchao ZHOU
1
;
Dingwen XU
1
Author Information
- Publication Type:Journal Article
- Keywords: SLC1A4 ；ovarian cancer；platinum resistance
- From: Chinese Journal of Modern Applied Pharmacy 2024;41(9):1204-1213
- CountryChina
- Language:Chinese
- Abstract: OBJECTIVE :To investigate the role of solute carrier family 1 member 4(SLC1A4) in platinum-based chemotherapy resistance in ovarian cancer. METHODS The expression of SLC1A4 in ovarian cancer or platinum-resistant ovarian cancer was analyzed by GEO and TCGA database analysis tools. The expression of SLC1A4 in platinum-treated ovarian cancer cell lines was analyzed by GEO database. The relation of SLC1A4 expression and overall survival(OS) or progression free survival(PFS) in ovarian cancer patients were analyzed by Kaplan Meier-plotter. Correlation between SLC1A4 gene effect and sensitivity to chemotherapeutic agents in ovarian cancer was analyzed through DepMap platform. Low expression of SLC1A4 mediates cisplatin resistance in ovarian cancer cells as verified by flow cytometry and tumor cell clone colony formation assays; prediction of microRNAs(miRNA) targeting SLC1A4 was conducted using TargetScan then validated their correlation in TCGA ovarian cancer samples. Used COREMINE tool to analyze the biological processes of SLC1A4 mediating chemoresistance in ovarian cancer. RESULTS SLC1A4 was significantly reduced in ovarian cancer patients and platinum-resistant ovarian cancer(P<0.05) and significantly correlated with OS and PFS in ovarian cancer patients(P<0.05). SLC1A4 expression was increased in ovarian cancer cells with platinum treatment. The genetic effect of SLC1A4 on ovarian cancer was positively correlated with platinum drug sensitivity. Overexpression of SLC1A4 increased cisplatin-induced apoptosis and reduced tumor cell colony formation in ovarian cancer cells. Hsa-let-7c-5p was targeted to SLC1A4 and significantly negatively correlated in samples from drug-resistant ovarian cancer patients. CONCLUSION Low expression of SLC1A4 mediates platinum drug resistance in ovarian cancer and is potentially associated with hsa-let-7c-5p regulation.
