Linc-KILH potentiates Notch1 signaling through inhibiting KRT19 phosphorylation and promotes the malignancy of hepatocellular carcinoma
| Autor: | Xiaoliang Xu, Chunfu Zhu, Siyuan Wu, Yue Fu, Zhijun Kong, Xiao Yun, Xudong Zhang, Zechuan Zhang, Cailin Xue, Xihu Qin |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
China Carcinoma Hepatocellular microvascular invasion Mice Nude Chromosomal translocation RAC1 Biology Applied Microbiology and Biotechnology Metastasis Cohort Studies 03 medical and health sciences Cell Line Tumor medicine Animals Humans long noncoding RNAs Receptor Notch1 Molecular Biology neoplasms Wnt Signaling Pathway Ecology Evolution Behavior and Systematics 030304 developmental biology Keratin-19 0303 health sciences Mice Inbred BALB C Liver Neoplasms Cell Biology hepatocellular carcinoma Middle Aged medicine.disease In vitro Long non-coding RNA digestive system diseases Cytoplasm Hepatocellular carcinoma Cancer research Phosphorylation Female RNA Long Noncoding Developmental Biology Research Paper |
| Zdroj: | International Journal of Biological Sciences |
| ISSN: | 1449-2288 |
| Popis: | Long noncoding RNAs (LncRNAs) are emerging as crucial regulators in the pathophysiological process of various tumors, including HCC. Here, we identify a novel lncRNA Linc-KILH (KRT19 interacting long noncoding RNA in hepatocellular carcinoma), which is significantly up-regulated in HCC tissues and positively correlated with larger tumor size, severer microvascular invasion, more intrahepatic metastasis and decreased survival of HCC patients. Silence of Linc-KILH remarkably inhibited the proliferation and metastasis abilities of KRT19-positive HCC cells in vitro and in vivo. Mechanistically, Linc-KILH interacts with KRT19 and then inhibits the phosphorylation of KRT19 on Ser35, thereby, enhancing the translocation of KRT19 from cytoplasm to membrane in KRT19 positive HCC cells. Additionally, we validated that KRT19 interacts with β-catenin but not RAC1 in HCC cells. Linc-KILH enhanced the interaction between β-catenin and KRT19 in cytoplasm and promoted the nuclear translocation of β-catenin in HCC cells. Furthermore, Linc-KILH could enhance the promoting function of KRT19 on Notch1 signaling with the existence of KRT19 in HCC cells. Collectively, we revealed that Linc-KILH exerts a vital function in KRT19 positive HCC progression and may likely be developed into an effective therapeutic target for HCC. |
| Databáze: | OpenAIRE |
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