Hypoxia-driven miR-1307-3p promotes hepatocellular carcinoma cell proliferation and invasion by modulating DAB2 interacting protein
| Autor: | Shuangjiang Chen, Runkun Liu, Hao Wang, Qingguang Liu |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
Carcinoma
Hepatocellular TOR Serine-Threonine Kinases Liver Neoplasms Cell Biology Pathology and Forensic Medicine Gene Expression Regulation Neoplastic MicroRNAs Cell Line Tumor Basic Helix-Loop-Helix Transcription Factors Tumor Microenvironment Humans RNA Long Noncoding Hypoxia Proto-Oncogene Proteins c-akt Cell Proliferation Neoplastic Processes Adaptor Proteins Signal Transducing |
| Zdroj: | Pathology, research and practice. 237 |
| ISSN: | 1618-0631 |
| Popis: | Hypoxia is a common feature of the solid tumor microenvironment that is presented as poor clinical outcomes in multiple tumor types, including HCC. Hypoxia stabilizes HIF-1α/HIF-2α, which then moves into the nucleus and binds with HIF-1β to form a transcription complex, thereby promoting the transcription of target genes, including mRNAs, miRNAs and lncRNAs to exert their biological functions. Here, through a series of functional assay, including hypoxia culture, MTT, colony-formation, Transwell, qRT-PCR and western blot, we confirmed that miR-1307-3p, as a novel hypoxia-responsive factor, can be directly transcribed by HIF-1α rather than HIF-2α. Hypoxia-driven miR-1307-3p facilitated proliferation and invasion of HCC cells via repressing DAB2IP. Moreover, under hypoxia microenvironment, DAB2IP, as a direct target of miR-1307-3p, was down-regulated to activate AKT/mTOR signaling to further maintain the expression level of HIF-1α, thereby forming a feedback loop between HIF-1α/miR-1307-3p and DAB2IP. Targeting miR-1307-3p/DAB2IP axis also modulated tumor growth and metastasis in vivo. In summary, there exists a feedback loop between HIF-1α/miR-1307-3p and DAB2IP in HCC. Targeting a vicious feedback loop between HIF-1α/miR-1307-3p and DAB2IP may be a promising strategy to combat HCC. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect