Lnc-PICSAR contributes to cisplatin resistance by miR-485-5p/REV3L axis in cutaneous squamous cell carcinoma

Dan Wang; Xiaoqiang Zhou; Jing Yin; Yang Zhou

doi:10.1515/biol-2020-0049

Lnc-PICSAR contributes to cisplatin resistance by miR-485-5p/REV3L axis in cutaneous squamous cell carcinoma

Open Life Sci. 2020 Jul 10;15(1):488-500. doi: 10.1515/biol-2020-0049. eCollection 2020.

Authors

Dan Wang¹, Xiaoqiang Zhou², Jing Yin³, Yang Zhou⁴

Affiliations

¹ Plastic Surgery Center, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214000, China.
² Department of Dermatology, Medical College of Shaoguan University, Shaoguan, 512026, China.
³ Department of Interventional Vascular, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214000, China.
⁴ Department of Dermatology, Yancheng First People's Hospital, Jiangsu Province, No.166 yulong west road, Yancheng, Jiangsu, 224001, China.

Abstract

Background: Dysregulation of long noncoding RNAs (lncRNAs) is associated with drug resistance in multiple cancers. We explored the roles of lncRNA p38 inhibited cutaneous squamous cell carcinoma-associated lincRNA (PICSAR) in cisplatin (DDP) resistance of cutaneous squamous cell carcinoma (CSCC).

Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to measure the expression of lnc-PICSAR, miR-485-5p and reversionless 3-like (REV3L) mRNA. The cell counting kit-8 (CCK-8) assay was conducted to evaluate DDP resistance and cell viability. The transwell assay was performed to determine cell migration and invasion. Western blot assay and immunohistochemistry (IHC) staining assay were carried out to measure protein levels. The dual-luciferase reporter assay was used to investigate the association between miR-485-5p and lnc-PICSAR or REV3L. Murine xenograft model was constructed to explore the function of lnc-PICSAR in vivo. The morphology of exosomes was analyzed by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA).

Results: Lnc-PICSAR was elevated in DDP-resistant CSCC cells. Lnc-PICSAR silencing suppressed cell viability, DDP resistance, migration and invasion in DDP-resistant CSCC cells. MiR-485-5p acted as a target of lnc-PICSAR, and miR-485-5p inhibition reversed the impacts of lnc-PICSAR silencing on DDP resistance and cell progression in DDP-resistant CSCC cells. Lnc-PICSAR promoted REV3L expression via sponging miR-485-5p. Moreover, REV3L overexpression overturned the effects of lnc-PICSAR on cell progression and DDP resistance. Lnc-PICSAR knockdown suppressed DDP resistance in vivo. In addition, lnc-PICSAR was increased in the exosomes derived from CSCC patients' serum and CSCC cells.

Conclusion: Lnc-PICSAR enhanced DDP resistance via miR-485-5p/REV3L axis in DDP-resistant CSCC cells. Besides, exosome-mediated lnc-PICSAR might be involved in the regulation of drug resistance in CSCC.

Keywords: CSCC; DDP resistance; REV3L; exosome; lnc-PICSAR; miR-485-5p.