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Lnc-PICSAR contributes to cisplatin resistance by miR-485-5p/REV3L axis in cutaneous squamous cell carcinoma
Dan Wang1, Xiaoqiang Zhou2, Jing Yin3
1Plastic Surgery Center, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214000, China.
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.
Insights
Long noncoding RNA PICSAR promotes cisplatin resistance in cutaneous squamous cell carcinoma by regulating the miR-485-5p/REV3L pathway. Exosomal PICSAR may also contribute to drug resistance in CSCC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Dysregulation of long noncoding RNAs (lncRNAs) is implicated in cancer drug resistance.
- Cutaneous squamous cell carcinoma (CSCC) exhibits resistance to cisplatin (DDP), a common chemotherapeutic agent.
Purpose of the Study:
- To investigate the role of lncRNA PICSAR in DDP resistance in CSCC.
- To elucidate the molecular mechanism underlying PICSAR's function in DDP-resistant CSCC.
Main Methods:
- Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assays.
- Cell counting kit-8 (CCK-8), transwell, and dual-luciferase reporter assays.
- Murine xenograft models and exosome analysis (TEM, NTA).
Main Results:
- Lnc-PICSAR expression was elevated in DDP-resistant CSCC cells and patient-derived exosomes.
- Silencing lnc-PICSAR reduced cell viability, DDP resistance, migration, and invasion.
- Lnc-PICSAR sponges miR-485-5p, leading to increased REV3L expression, which promotes CSCC progression and DDP resistance.
- Lnc-PICSAR knockdown inhibited DDP resistance in vivo.
Conclusions:
- Lnc-PICSAR enhances DDP resistance in CSCC through the miR-485-5p/REV3L axis.
- Exosome-mediated lnc-PICSAR may play a role in CSCC drug resistance, suggesting potential diagnostic or therapeutic targets.
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