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Published on: March 27, 2020
Long non-coding RNA PICSAR knockdown inhibits the progression of cutaneous squamous cell carcinoma by regulating
Xiaoyan Lu1, Quan Gan1, Caibin Gan1
1Department of Dermatology, Xinxiang Central Hospital, Xinxiang, Henan, China.
Aims:
The purpose of this study was to explore the precise role and mechanism of p38 inhibiting cutaneous squamous cell carcinoma associated lincRNA (PICSAR) in CSCC.
Materials And Methods:
The expression levels of PICSAR, microRNA-125b (miR-125b) and yes-associated protein1 (YAP1) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, apoptosis and invasion were evaluated by Cell Counting Kit-8 (CCK-8) assay, flow cytometry, transwell assay, respectively. The interaction between miR-125b and PICSAR or YAP1 was predicted by bioinformatics software and confirmed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Western blot was employed to detect the protein expression of YAP1. The mice xenograft model was established to investigate the role of PICSAR in vivo.
Key Findings:
PICSAR was upregulated in CSCC tissues and cells. PICSAR knockdown inhibited cell proliferation and invasion and induced apoptosis in CSCC cells. Moreover, miR-125b could directly bind to PICSAR and its inhibition reversed the effect of PICSAR knockdown on proliferation, invasion and apoptosis in CSCC cells. In addition, YAP1 was a direct target of miR-125b and its overexpression attenuated the anti-cancer role of miR-125b in CSCC cells. Furthermore, YAP1 expression was positively regulated by PICSAR and negatively regulated by miR-125b. Besides, interference of PICSAR suppressed tumor growth by upregulating miR-125b and downregulating YAP1.
Significance:
PICSAR knockdown suppressed cell proliferation and invasion and promoted apoptosis in CSCC cells by regulating miR-125b/YAP1 axis, providing new sights for treatment of CSCC.
Insights
Knocking down p38 inhibiting cutaneous squamous cell carcinoma associated lincRNA (PICSAR) in cutaneous squamous cell carcinoma (CSCC) inhibits cancer progression. PICSAR regulates the miR-125b/YAP1 axis, offering a potential therapeutic target for CSCC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Cutaneous squamous cell carcinoma (CSCC) is a prevalent skin cancer.
- Long non-coding RNAs (lncRNAs) play critical roles in cancer development.
- The specific function of PICSAR in CSCC remains largely unknown.
Purpose of the Study:
- To elucidate the role and mechanism of p38 inhibiting cutaneous squamous cell carcinoma associated lincRNA (PICSAR) in CSCC.
- To investigate the regulatory pathway involving PICSAR, miR-125b, and YAP1 in CSCC.
Main Methods:
- Quantitative real-time polymerase chain reaction (qRT-PCR) to measure PICSAR, miR-125b, and YAP1 expression.
- Cell proliferation (CCK-8), apoptosis (flow cytometry), and invasion (Transwell) assays.
- Bioinformatics, dual-luciferase reporter, and RNA immunoprecipitation (RIP) assays to confirm molecular interactions.
- Western blot for YAP1 protein levels and a mice xenograft model for in vivo validation.
Main Results:
- PICSAR expression was significantly upregulated in CSCC tissues and cells.
- PICSAR knockdown inhibited CSCC cell proliferation and invasion while promoting apoptosis.
- PICSAR directly interacted with miR-125b, and miR-125b targeted YAP1.
- PICSAR positively regulated YAP1, while miR-125b negatively regulated it.
- Interference with PICSAR suppressed tumor growth by modulating the miR-125b/YAP1 axis.
Conclusions:
- PICSAR knockdown exerts anti-cancer effects in CSCC by regulating the miR-125b/YAP1 axis.
- The PICSAR/miR-125b/YAP1 pathway represents a novel therapeutic target for CSCC treatment.
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