M6A-mediated up-regulation of LncRNA LIFR-AS1 enhances the progression of pancreatic cancer via miRNA-150-5p/ VEGFA/Akt signaling
| Autor: | Hui-fen Li, Yong-Gang Hong, Liang-Kai Hu, Yuan-ping Tao, Zhi-ping Huang, Xuan-Fu Xu, Jian-Qing Chen, Hao Zheng |
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| Rok vydání: | 2021 |
| Předmět: |
Vascular Endothelial Growth Factor A
Adenosine Leukemia Inhibitory Factor Receptor alpha Subunit Biology medicine.disease_cause Phosphatidylinositol 3-Kinases Pancreatic cancer Cell Line Tumor microRNA medicine Humans Molecular Biology Protein kinase B PI3K/AKT/mTOR pathway Cell Proliferation Gene knockdown Cell Biology Methyltransferases medicine.disease Up-Regulation Pancreatic Neoplasms Vascular endothelial growth factor A MicroRNAs Tumor progression Cancer research RNA Long Noncoding Carcinogenesis Proto-Oncogene Proteins c-akt Developmental Biology Research Paper Signal Transduction |
| Zdroj: | Cell Cycle |
| DOI: | 10.6084/m9.figshare.16823079.v1 |
| Popis: | N6-methyladenosine (m6A) modification, the most abundant internal methylation of eukaryotic RNA transcripts, is critically implicated in RNA processing. There is extensive evidence indicating that long non-coding RNAs (lncRNAs) serve as key regulators of oncogenesis and tumor progression in humans. Through prior study has assessed that LIFR-AS1 plays a key role in various kinds of malignant tumors. However, the exact role of m6A induced LIFR-AS1 in pancreatic cancer (PC) and its potential molecular mechanisms remain largely unknown. In this study, we determined that PC cell lines and tumors exhibit increased LIFR-AS1 expression that correlates with larger tumor size, lymph node metastasis, and more advanced TNM stage. Functionally, loss-of-function studies indicated that LIFR-AS1 knockdown decreased the proliferation, migration, and invasion of PC cells in vitro. Mechanistically, we found that METTL3 induced m6A hyper-methylation on the 3′ UTR of LIFR-AS1 to enhance its mRNA stability and LIFR-AS1 could directly interact with miR-150-5p, thereby indirectly up-regulating VEGFA expressions within cells. Through rescue experiments, we were able to confirm that the unfavorable impact of LIFR-AS1 knockdown on VEGFA /PI3K/Akt Signaling could be reversed via the inhibition of miR-150-5p expression. Together, these findings indicate that a noval m6A-LIFR-AS1 axis promotes PC progression at least in part via regulation of the miR-150-5p/VEGFA axis, indicating that this regulatory axis may be a viable clinical target for the treatment of PC. |
| Databáze: | OpenAIRE |
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