TFAP2A potentiates lung adenocarcinoma metastasis by a novel miR-16 family/TFAP2A/PSG9/TGF-β signaling pathway.

Abstract

Transcription factor AP-2α (TFAP2A) was previously regarded as a critical regulator during embryonic development, and its mediation in carcinogenesis has received intensive attention recently. However, its role in lung adenocarcinoma (LUAD) has not been fully elucidated. Here, we tried to investigate TFAP2A expression profiling, clinical significance, biological function and molecular underpinnings in LUAD. We proved LUAD possessed universal TFAP2A high expression, indicating a pervasively poorer prognosis in multiple independent datasets. Then we found TFAP2A was not indispensable for LUAD proliferation, and exogenous overexpression even caused repression. However, we found TFAP2A could potently promote LUAD metastasis possibly by triggering epithelial-mesenchymal transition (EMT) in vitro and in vivo. Furthermore, we demonstrated TFAP2A could transactivate Pregnancy-specific glycoprotein 9 (PSG9) to enhance transforming growth factor β (TGF-β)-triggering EMT in LUAD. Meanwhile, we discovered suppressed post-transcriptional silencing of miR-16 family upon TFAP2A partly contributed to TFAP2A upregulation in LUAD. In clinical specimens, we also validated cancer-regulating effect of miR-16 family/TFAP2A/PSG9 axis, especially for lymph node metastasis of LUAD. In conclusion, we demonstrated that TFAP2A could pivotally facilitate LUAD progression, possibly through a novel pro-metastasis signaling pathway (miR-16 family/TFAP2A/PSG9/ TGF-β).

• Authors: Yanlu Xiong, Yangbo Feng, Jinbo Zhao, Jie Lei, Tianyun Qiao, Yongsheng Zhou, Qiang Lu, Tao Jiang, Lintao Jia, Yong Han
• Journal: Cell death & disease (Cell Death Dis) Vol. 12 Issue 4 Pg. 352 (04 06 2021) ISSN: 2041-4889 [Electronic] England
• PMID: 33824285 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MIRN16 microRNA, human
• MicroRNAs
• TFAP2A protein, human
• Transcription Factor AP-2

Topics

• Adenocarcinoma of Lung (genetics, metabolism, pathology)
• Cell Line, Tumor
• Cell Movement (physiology)
• Cell Proliferation (physiology)
• Gene Expression Regulation, Neoplastic (genetics)
• Humans
• Lung Neoplasms (metabolism, pathology)
• Lymphatic Metastasis (pathology)
• MicroRNAs (genetics)
• Neoplasm Metastasis (genetics, pathology)
• Transcription Factor AP-2 (genetics)
• Up-Regulation