MicroRNA-125b exerts antitumor functions in cutaneous squamous cell carcinoma by targeting the STAT3 pathway.

MicroRNA-125b (miR-125b) is downregulated in human cutaneous squamous cell carcinoma (CSCC). However, its function in CSCC has yet to be extensively explored. Here, we analyze the relationship between signal transducer and activator of transcription 3 (STAT3) and miR-125b in CSCC. Western blotting and quantitative RT-PCR were used to determine the expression of the miR-125b-STAT3 axis in human CSCC tissues and cell lines. The direct regulatory effect of miR-125b on STAT3 expression was assessed using a luciferase reporter gene assay and RNA immunoprecipitation assay. The MTT assay and flow cytometry were used to determine the role of the miR-125b-STAT3 axis in CSCC cell proliferation and apoptosis. MiR-125b expression levels were significantly lower in CSCC cell lines and tissues than in normal cell lines and tissues. STAT3 was identified as the direct target of miR-125b. Upregulation of miR-125b and downregulation of STAT3 suppressed cell proliferation and promoted cell apoptosis. Cyclin D1 and Bcl2 were identified as the downstream targets of the miR-125-STAT3 axis. Our findings indicate that miR-125b acts as a tumor suppressor in CSCC by targeting the STAT3 pathway. This observation increases our understanding of the molecular mechanisms of CSCC. Therapies aimed at activating miR-125b or inhibiting STAT3 signaling should be explored as potential treatments for CSCC.

Tian K ，Liu W ，Zhang J ，Fan X ，Liu J ，Zhao N ，Yao C ，Miao G ... -  《-》

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 ... -  《-》

MicroRNA-125b down-regulates matrix metallopeptidase 13 and inhibits cutaneous squamous cell carcinoma cell proliferation, migration, and invasion.

Xu N ，Zhang L ，Meisgen F ，Harada M ，Heilborn J ，Homey B ，Grandér D ，Ståhle M ，Sonkoly E ，Pivarcsi A ... -  《-》

microRNA-214 Prevents Traits of Cutaneous Squamous Cell Carcinoma via VEGFA and Bcl-2.

Ma X ，Wu D ，Zhang X ，Shao X ，Hu G ... -  《-》

GRIM-19 represses the proliferation and invasion of cutaneous squamous cell carcinoma cells associated with downregulation of STAT3 signaling.

The gene associated with retinoid-interferon-induced mortality-19 (GRIM-19) has been identified as a tumor suppressor in many human cancers. However, little is known about the role of GRIM-19 in cutaneous squamous cell carcinoma (CSCC). Here, we aimed to investigate the potential function of GRIM-19 in CSCC and explore the underlying molecular mechanisms. We found that GRIM-19 protein and transcript levels were significantly decreased in CSCC cell lines. Overexpression of GRIM-19 suppressed the proliferation and invasion of CSCC cells, whereas knockdown of GRIM-19 promoted the proliferation and invasion of CSCC cells. Also, we found that overexpression of GRIM-19 inhibited the phosphorylation and transcription activity of the signal transducer and activator of transcription 3 (STAT3). Overexpression of GRIM-19 also suppressed the expression of STAT3 target genes, including cyclin D1, Bcl-2 and metal matrix proteinase 2. By contrast, knockdown of GRIM-19 showed the opposite effect. Moreover, suppression of STAT3 significantly attenuated the effect of GRIM-19 knockdown on induction of proliferation, invasion, and STAT3 target genes in CSCC cells. Taken together, our data show that GRIM-19 suppresses the proliferation and invasion of CSCC cells associated with downregulation of STAT3 signaling, suggesting a tumor suppressive role of GRIM-19 in CSCC. Our study suggests that decreased expression of GRIM-19 may contribute to the development and progression of CSCC and that GRIM-19 may serve as a potential therapeutic target for CSCC treatment.

Wu N ，Hui H ，Cui L ，Yang F ... -  《-》