Long Noncoding RNA PICSAR Promotes Growth of Cutaneous Squamous Cell Carcinoma by Regulating ERK1/2 Activity.

Keratinocyte-derived cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer, and its incidence is increasing globally. Long noncoding RNAs (lncRNA) are involved in various biological processes, and their role in cancer progression is emerging. Whole transcriptome analysis of cSCC cells (n = 8) and normal human epidermal keratinocytes (n = 4) revealed overexpression of long intergenic ncRNA (LINC00162) in cSCC cells. The expression of LINC00162 in cSCC cells was upregulated by inhibition of the p38α and p38δ mitogen-activated protein kinases. Analysis of tissue sections by RNA in situ hybridization showed that LINC00162 is specifically expressed by tumor cells in cSCCs but not by keratinocytes in normal skin in vivo. Knockdown of LINC00162 inhibited proliferation and migration of cSCC cells, and suppressed the growth of human cSCC xenografts in vivo. Furthermore, knockdown of LINC00162 inhibited extracellular signal-regulated kinase 1/2 activity and upregulated expression of dual specificity phosphatase 6 (DUSP6) in cSCC cells. Based on these observations, LINC00162 was named p38 inhibited cutaneous squamous cell carcinoma associated lincRNA (PICSAR). Our results provide mechanistic evidence for the role of PICSAR in promoting cSCC progression via activation of extracellular signal-regulated kinase 1/2 signaling pathway by downregulating DUSP6 expression. These results also identify PICSAR as a biomarker and putative therapeutic target in cSCC.

Piipponen M ，Nissinen L ，Farshchian M ，Riihilä P ，Kivisaari A ，Kallajoki M ，Peltonen J ，Peltonen S ，Kähäri VM ... -  《-》

Long non-coding RNA PICSAR knockdown inhibits the progression of cutaneous squamous cell carcinoma by regulating miR-125b/YAP1 axis.

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. 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. 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. 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.

Lu X ，Gan Q ，Gan C ，Zheng Y ，Cai B ，Li X ，Li D ，Yin G ... -  《-》

p53-Regulated Long Noncoding RNA PRECSIT Promotes Progression of Cutaneous Squamous Cell Carcinoma via STAT3 Signaling.

Long noncoding RNAs (lncRNAs) have emerged as putative biomarkers and therapeutic targets in cancer. The role of lncRNA LINC00346 in cutaneous squamous carcinoma (cSCC) was examined. The expression of LINC00346 was up-regulated in cSCC cells compared with normal human epidermal keratinocytes. Elevated expression of LINC00346 was noted in tumor cells in cSCC tissue sections in vivo, as compared with cSCC in situ, and actinic keratosis by RNA in situ hybridization; and the expression in seborrheic keratosis and normal skin was very low. Immunohistochemical analysis of cSCC tissue sections and functional assays of cSCC cells in culture showed that LINC00346 expression is down-regulated by p53. Knockdown of LINC00346 inhibited invasion of cSCC cells in culture and suppressed growth of human cSCC xenografts in vivo. Knockdown of LINC00346 inhibited expression of activated STAT3 and resulted in down-regulation of the expression of matrix metalloproteinase (MMP)-1, MMP-3, MMP-10, and MMP-13. Based on these observations LINC00346 was named p53 regulated carcinoma-associated STAT3-activating long intergenic non-protein coding transcript (PRECSIT). These results identify PRECSIT as a new p53-regulated lncRNA, which promotes progression of cSCC via STAT3 signaling.

Piipponen M ，Nissinen L ，Riihilä P ，Farshchian M ，Kallajoki M ，Peltonen J ，Peltonen S ，Kähäri VM ... -  《-》

Complement factor H: a biomarker for progression of cutaneous squamous cell carcinoma.

Riihilä PM ，Nissinen LM ，Ala-Aho R ，Kallajoki M ，Grénman R ，Meri S ，Peltonen S ，Peltonen J ，Kähäri VM ... -  《-》

EphB2 Promotes Progression of Cutaneous Squamous Cell Carcinoma.

Farshchian M ，Nissinen L ，Siljamäki E ，Riihilä P ，Toriseva M ，Kivisaari A ，Ala-Aho R ，Kallajoki M ，Veräjänkorva E ，Honkanen HK ，Heljasvaara R ，Pihlajaniemi T ，Grénman R ，Peltonen J ，Peltonen S ，Kähäri VM ... -  《-》