KRT14 knockdown reduces cisplatin resistance by lowering LRP11 expression levels in cisplatin-resistant ovarian cancer cell lines.

BACKGROUND: Platinum resistance is a major cause of mortality in patients with advanced ovarian cancer. Understanding the mechanisms underlying this resistance is essential for developing effective treatments to improve patient survival. Therefore, this study aimed to explore the role and mechanisms of keratin 14 (KRT14) in regulating cisplatin resistance in ovarian cancer. METHODS: We utilized quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting to measure messenger RNA (mRNA) and protein expression levels, respectively. Cisplatin-resistant cell lines (SK-OV-3/DDP and A2780/DDP) were transfected with small interfering RNA (siRNA) targeting KRT14 (si-KRT14) or a plasmid containing low-density lipoprotein receptor-related protein 11 (LRP11) to knock down KRT14 or overexpress LRP11, respectively. Differentially expressed mRNAs were identified using Illumina RNA sequencing. Cell viability and half-maximal inhibitory concentration (IC(50)) values were determined via cell counting kit-8 (CCK-8) assays, while apoptosis was assessed using flow cytometry and Hoechst 33258 staining. RESULTS: KRT14 mRNA and protein levels were significantly higher in SK-OV-3/DDP and A2780/DDP cells compared with their parental counterparts. KRT14 knockdown reduced the IC(50) values, increased apoptosis, and decreased the levels of the multidrug resistance (MDR)-related proteins P-glycoprotein (P-gp) and MDR-associated protein 1 (MRP1). KRT14 knockdown in SK-OV-3/DDP and A2780/DDP cells revealed 24 differentially expressed mRNAs. Further analysis revealed that KRT14 knockdown notably reduced LRP11 expression. LRP11 overexpression increased IC(50) values, suppressed apoptosis, and enhanced MDR-related protein expression, thus counteracting the effects of KRT14 knockdown. CONCLUSIONS: Cisplatin-resistant ovarian cancer cell lines revealed elevated KRT14 expression. KRT14 knockdown reduced cisplatin resistance by lowering LRP11 expression. Therefore, KRT14 may play a crucial role in mediating cisplatin resistance in ovarian cancer.