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

Yingying Jiang; Haiyan Guo; Tong Tong; Fei Xie; Xing Qin; Xiaoning Wang; Wantao Chen; Jianjun Zhang

doi:10.1016/j.ymthe.2021.06.006

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

Mol Ther. 2022 Jan 5;30(1):448-467. doi: 10.1016/j.ymthe.2021.06.006. Epub 2021 Jun 8.

Authors

Yingying Jiang¹, Haiyan Guo², Tong Tong³, Fei Xie³, Xing Qin³, Xiaoning Wang³, Wantao Chen⁴, Jianjun Zhang⁵

Affiliations

¹ Department of Oral and Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China; Department of Dentistry, Affiliated Hospital of Weifang Medical University, Weifang 261031, P.R. China.
² Department of Clinical Laboratory, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201999, P.R. China.
³ Department of Oral and Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China.
⁴ Department of Oral and Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, Shanghai 200011, P.R. China. Electronic address: chenwantao196323@sjtu.edu.cn.
⁵ Department of Oral and Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, Shanghai 200011, P.R. China. Electronic address: zjjshuobo@163.com.

Abstract

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.

Keywords: DNA repair; cisplatin resistance; head and neck squamous cell carcinoma; lnc-POP1-1; long noncoding RNA; minichromosome maintenance deficient 5; specificity protein 1; ubiquitination; vomeronasal type-1 receptor 5.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis Regulatory Proteins / genetics
Cell Cycle Proteins / genetics
Cell Line, Tumor
Cisplatin / pharmacology
Drug Resistance, Neoplasm / genetics
Gene Expression Regulation, Neoplastic
Head and Neck Neoplasms* / drug therapy
Head and Neck Neoplasms* / genetics
Humans
RNA, Long Noncoding* / genetics
Ribonucleoproteins
Squamous Cell Carcinoma of Head and Neck / drug therapy
Squamous Cell Carcinoma of Head and Neck / genetics

Substances

Apoptosis Regulatory Proteins
Cell Cycle Proteins
MCM5 protein, human
POP1 protein, human
RNA, Long Noncoding
Ribonucleoproteins
Cisplatin