TGF-β-induced STAT3 overexpression promotes human head and neck squamous cell carcinoma invasion and metastasis through malat1/miR-30a interactions.

Aberrant signal transducer and activator of transcription 3 (STAT3) signaling is a critical factor that drives the invasion and metastasis of head and neck squamous cell carcinoma (HNSCC). However, the underlying mechanisms of STAT3 overexpression and regulation of HNSCC metastasis remain unknown. In the current study, we demonstrated that upregulated TGF-β may promote epithelial-mesenchymal transition (EMT) through STAT3 activation. In addition, we explored the contributions of STAT3 to HNSCC with a specific focus on its transcriptional regulation and its interaction with the long noncoding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (malat1). Chromatin immunoprecipitation (ChIP) and luciferase reporter assays revealed that STAT3 could bind to the malat1 promoter region and transcriptionally activate malat1 expression; then, malat1 interacted reciprocally with miR-30a, inducing EMT and accelerating HNSCC metastasis. In summary, our discoveries illuminate how aberrant STAT3 activation confers an oncogenic function in HNSCC and therefore may provide a theoretical foundation for STAT3 as a therapeutic target in HNSCC.

Wang Y ，Wu C ，Zhang C ，Li Z ，Zhu T ，Chen J ，Ren Y ，Wang X ，Zhang L ，Zhou X ... -  《-》

p53-targeted lincRNA-p21 acts as a tumor suppressor by inhibiting JAK2/STAT3 signaling pathways in head and neck squamous cell carcinoma.

Jin S ，Yang X ，Li J ，Yang W ，Ma H ，Zhang Z ... -  《Molecular Cancer》

Targeting STAT3/miR-21 axis inhibits epithelial-mesenchymal transition via regulating CDK5 in head and neck squamous cell carcinoma.

Sun SS ，Zhou X ，Huang YY ，Kong LP ，Mei M ，Guo WY ，Zhao MH ，Ren Y ，Shen Q ，Zhang L ... -  《Molecular Cancer》

Disrupting MALAT1/miR-200c sponge decreases invasion and migration in endometrioid endometrial carcinoma.

Endometrioid endometrial carcinoma (EEC) is the most common gynecologic malignancy around the world. Epithelial-to-mesenchymal transition (EMT) is a core process during EEC cell invasion. The abnormal expression of the long noncoding RNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) or miR-200 family members were shown to facilitate EMT in multiple human cancers, but the regulatory mechanism by which MALAT1 and miR-200 act remains unknown. Previous studies have shown that miR-200 family members are enriched in EEC as well as melanoma and some ovarian carcinomas. In the present study, we first showed that miR-200c levels were higher in most EEC specimens than in non-tumor tissues, while MALAT1 levels were lower. Moreover, we found that miR-200c bound directly to MALAT1 using luciferase reporter and qRT-PCR assays. MALAT1 and miR-200c are reciprocally repressed, and TGF-β increased MALAT1 expression by inhibiting miR-200c. When the interaction between miR-200c/MALAT1 was interrupted, the invasive capacity of EEC cells was decreased and EMT markers expression were altered in vitro. A xenograft tumor model was used to show that targeting the miR-200c/MALAT1 axis inhibited EEC growth and EMT-associated protein expression in vivo. In summary, miR-200c/MALAT1 axis is a target with therapeutic potential in EEC. However, different expression model of miR-200c and MALAT1 in EEC with that in other organ carcinomas needs further mechanism researches.

Li Q ，Zhang C ，Chen R ，Xiong H ，Qiu F ，Liu S ，Zhang M ，Wang F ，Wang Y ，Zhou X ，Xiao G ，Wang X ，Jiang Q ... -  《-》

miR-300 inhibits epithelial to mesenchymal transition and metastasis by targeting Twist in human epithelial cancer.

Yu J ，Xie F ，Bao X ，Chen W ，Xu Q ... -  《Molecular Cancer》