lncRNA lnc-POP1-1 upregulated by VN1R5 promotes cisplatin resistance in head and neck squamous cell carcinoma through interaction with MCM5

• DOI: 10.1016/j.ymthe.2021.06.006
• Publication Date: 2021-06-08T03:54:01Z
• Authors: Yingying Jiang; Haiyan Guo; Tong Tong; Fei Xie; Xing Qin; Xiaoning Wang; Wantao Chen; Jianjun Zhang
• Keywords: 0303 health sciences; Squamous Cell Carcinoma of Head and Neck; Cell Cycle Proteins; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; Ribonucleoproteins; Drug Resistance, Neoplasm; Head and Neck Neoplasms; Cell Line, Tumor; Humans; RNA, Long Noncoding; Cisplatin; Apoptosis Regulatory Proteins

Cisplatin resistance is a major therapeutic challenge in advanced head and neck squamous cell carcinoma (HNSCC). Here, we aimed to investigate the key signaling pathway for cisplatin resistance in HNSCC cells. Vomeronasal type-1 receptor 5 (VN1R5) was identified as a cisplatin resistance-related protein and was highly expressed in cisplatin-resistant HNSCC cells and tissues. The long noncoding RNA (lncRNA) lnc-POP1-1 was confirmed to be a downstream target induced by VN1R5. VN1R5 transcriptionally regulated lnc-POP1-1 expression by activating the specificity protein 1 (Sp1) transcription factor via the cyclic AMP (cAMP)/protein kinase A (PKA) pathway. VN1R5 promoted cisplatin resistance in HNSCC cells in a lnc-POP1-1-dependent manner. Mechanistically, lnc-POP1-1 bound to the minichromosome maintenance deficient 5 (MCM5) protein directly and decelerated MCM5 degradation by inhibiting ubiquitination of the MCM5 protein, which facilitated the repair of DNA damage caused by cisplatin. In summary, we identified the cisplatin resistance-related protein VN1R5 and its downstream target lnc-POP1-1. Upon upregulation by VN1R5, lnc-POP1-1 promotes DNA repair in HNSCC cells through interaction with MCM5 and deceleration of its degradation.