Long non-coding RNA HCP5 functions as a sponge of miR-29b-3p and promotes cell growth and metastasis in hepatocellular carcinoma through upregulating DNMT3A
Autor: | Tu Dai, Xiaoming Ai, Yongping Zhou, Kuan Li, Fangming Chen, Zhiyuan Hua, Hong Wang, Hao Wang, Wuyang Bian |
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Rok vydání: | 2020 |
Předmět: |
Male
Aging Carcinoma Hepatocellular Epithelial-Mesenchymal Transition Apoptosis Biology medicine.disease_cause Metastasis DNA Methyltransferase 3A Cell Movement Cell Line Tumor medicine Humans metastasis Neoplasm Invasiveness DNA (Cytosine-5-)-Methyltransferases Neoplasm Metastasis Phosphorylation Protein kinase B lncRNA HCP5 Aged Cell Proliferation Gene knockdown miR-29b-3p Base Sequence Cell growth Liver Neoplasms Cell Biology hepatocellular carcinoma Middle Aged medicine.disease Long non-coding RNA digestive system diseases Up-Regulation Gene Expression Regulation Neoplastic MicroRNAs Hepatocellular carcinoma Cancer research Disease Progression DNMT3A Female RNA Long Noncoding Carcinogenesis Proto-Oncogene Proteins c-akt Research Paper |
Zdroj: | Aging (Albany NY) |
ISSN: | 1945-4589 |
Popis: | Background: Multiple researches have revealed that long non-coding RNA (lncRNAs) served as regulatory factor in modulating tumorigenesis of hepatocellular carcinoma (HCC). In this study, we demonstrated that lncRNA HCP5 was a tumor promoting factor of HCC, and the molecular mechanism of HCP5 has been elucidated at length.Methods: BrdU, transwell assay and flow cytometry were exerted to estimate cell growth, metastasis, invasion and apoptosis of HCC in vitro. Animal studies were performed the effect of HCP5 in vivo. Furthermore, we identified that miR-29b-3p interacted with HCP5 or DNA methyltransferase 3A (DNMT3A) using dual luciferase assay. qRT-PCR, western blot, BrdU, tanswell and flow cytometry assays were used to investigate the correlation of HCP5/miR-29b-3p/DNMT3A axis. Results: In present research, we elaborated that HCP5 was overexpressed in HCC tissues and cell lines, and this phenomenon was even obvious in metastatic and recurrent cases. Knockdown of HCP5 significantly alleviated cell growth, metastasis and invasion through preventing apoptosis and activating EMT progress. Moreover, miR-29b-3p has been identified as a negatively regulatory target gene of HCP5, which served as tumor suppressor of HCC to prevent cell proliferation, migration and invasion. Subsequently, DNMT3A was found as a downstream regulatory factor of miR-29b-3p, of which study found that a participated element of HCC progression by activating AKT phosphorylation.Conclusion: Generally, our study elucidated for the first time that HCP5 plays a crucial role in HCC via HCP5/ miR-29b-3p/DNMT3A/AKT axis and demonstrated a novel diagnostic and therapeutic strategy with potentiality. |
Databáze: | OpenAIRE |
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