LncRNA UCA1 promotes migration and invasion in pancreatic cancer cells via the Hippo pathway.

Although overexpression of the long non-coding RNA (lncRNA) UCA1 has been implicated in several human cancers, its biological function in pancreatic cancer remains to be clarified. In this study, we reported that UCA1 expression was significantly increased in pancreatic cancer tissues and correlated with clinicopathological features, tumor stage, and poorer patient outcome. We further showed that UCA1 promoted cell migration and invasion of pancreatic cancer cells. Importantly, we found that UCA1 overexpression inhibited YAP phosphorylation, and increased YAP expression. Mechanistically, UCA1 interacted with MOB1, Lats1, and YAP, forming shielding composites. Moreover, we demonstrated that UCA1 increased YAP nuclear localization and stabilization, and improved TEAD luciferase activity. In turn, YAP promotes UCA1 expression. Collectively, the present study provides insights into the mechanistic regulation of UCA1 promoting pancreatic cancer progression through the Hippo signaling pathway. UCA1 may serve as a candidate biomarker for poor prognosis and a target for new pancreatic cancer therapies.

Zhang M ，Zhao Y ，Zhang Y ，Wang D ，Gu S ，Feng W ，Peng W ，Gong A ，Xu M ... -  《BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE》

Study on mechanism about long noncoding RNA MALAT1 affecting pancreatic cancer by regulating Hippo-YAP signaling.

By investigating the migration and invasion ability in pancreatic cancer, this study probed into the lncRNA MALAT1 molecular mechanism on Hippo-YAP signaling. The expression of lncRNA MALAT1 in PC tissues and cells was detected by qRT-PCR and Western blot. The effect of si-MALAT1 on proliferation was determined by CCK-8 assay. Cell apoptosis, migration, and invasion were respectively detected by flow cytometry assay, wound healing assay, and transwell assay. Western blot and immunohistochemistry were successively used for detecting LATS1 and YAP1 expression in pancreatic cancer tissues. The microarray analysis determined that lncRNA MALAT1 in pancreatic cancer was highly expressed. LncRNA MALAT1 presented an extremely high expression level in pancreatic cancer tissues and cells. After transfected with si-MALAT1, the proliferation of AsPC-1 cells decreased, induce apoptosis of AsPC-1 cells, and migration and invasion ability were reduced. The tendency of LATS1 expression level was down-regulated and YAP1 show the opposite trend in the Hippo-YAP signaling. The in vivo assay was found that the tumor to be small in size and volume, and the expression of Ki-67 was decreased. High expression of lncRNA MALAT1 in PC disorder the proliferation, apoptosis, and migration and invasion ability via influence Hippo-YAP signaling pathway.

Zhou Y ，Shan T ，Ding W ，Hua Z ，Shen Y ，Lu Z ，Chen B ，Dai T ... -  《-》

Linc-RoR promotes proliferation, migration, and invasion via the Hippo/YAP pathway in pancreatic cancer cells.

Large intergenic noncoding RNA regulator of reprogramming (Linc-RoR) was first identified as a regulator to increase the emergence of induced pluripotent stem cells through reprogramming differentiated cells and is abnormal expression in a variety of malignant tumors. However, the function of Linc-RoR in pancreatic cancer progression needs further clarification. The data from this study demonstrated that Linc-RoR knockdown suppressed cell proliferative capacity and colony formation, while Linc-RoR overexpression promoted these behaviors. In particular, Linc-RoR overexpression promoted the level of mesenchymal markers, inhibited the expression of epithelial markers, as well as enhanced pancreatic cancer cells migration and invasion, whereas Linc-RoR knockdown inhibited the expression of mesenchymal markers, promoted the expression of epithelial markers, as well as weakened pancreatic cancer cells migration and invasion. Further study revealed that Linc-RoR knockdown brought about a significant fall in YAP phosphorylation and a rise in total YAP, while Linc-RoR overexpression produced the opposite results. Specifically, Linc-RoR promoted YAP in the cytoplasm into the nucleus. Taken together, we conjectured that Linc-RoR promoted proliferation, migration, and invasion of pancreatic cancer cells by activating the Hippo/YAP pathway. YAP might be an underlying target of Linc-RoR and mediate epithelial-mesenchymal transition (EMT) in pancreatic cancer (PC); thus, Linc-RoR might be a very meaningful biomarker for PC.

Chen W ，Wang H ，Liu Y ，Xu W ，Ling C ，Li Y ，Liu J ，Chen M ，Zhang Y ，Chen B ，Gong A ，Xu M ... -  《-》

TNFAIP8 regulates Hippo pathway through interacting with LATS1 to promote cell proliferation and invasion in lung cancer.

TNFAIP8 is associated with prognosis of several human malignancies. However, the molecular mechanism of TNFAIP8 in lung cancer remains unknown. In our study, we found TNFAIP8 could enhance TEAD luciferase activity and inhibits the activity of Hippo pathway. TNFAIP8 also increased cyclin D1, CDK6, and decreased p27 in lung cancer cells. In addition, TNFAIP8 increased total YAP protein and promoted nuclear localization of YAP. More importantly, YAP depletion blocked the role of TNFAIP8 on cell cycle-related proteins and TEAD luciferase activity, revealing that TNFAIP8 regulates Hippo pathway in a YAP-dependend manner. Further experiments identified that TNFAIP8 depletion enhanced LATS1 phosphorylation and TNFAIP8 overexpression decreased phosphorylated LAST1 level. LATS1 siRNA treatment reversed the effects of TNFAIP8 plasmid or siRNA on cell cycle proteins. Besides, immunofluorescence and co-immunoprecipitation demonstrated the interaction between TNFAIP8 and LATS1 in H460 and H1299 cells, suggesting that TNFAIP8 regulates Hippo signaling through its interaction with LATS1. Colony formation assays and transwell assays showed that YAP or LATS1 depletion reversed the positive effect of TNFAIP8 on cell proliferation and invasion. TNFAIP8 overexpression could increase MMP-7 and TNFAIP8 depletion could decrease MMP-7 at both protein and mRNA levels, without significant changes of E-cadherin, N-cadherin, and Vimentin. Collectively, the present study provides a novel finding that TNFAIP8 regulates Hippo pathway through interacting with LATS1 to promote cell proliferation and invasion in lung cancer. TNFAIP8 may serve as a candidate biomarker for poor prognosis and a target for new therapies.

Han Y ，Tang Z ，Zhao Y ，Li Q ，Wang E ... -  《-》

Upregulation of miR-181c contributes to chemoresistance in pancreatic cancer by inactivating the Hippo signaling pathway.

Chen M ，Wang M ，Xu S ，Guo X ，Jiang J ... -  《Oncotarget》