TFAP2A potentiates lung adenocarcinoma metastasis by a novel miR-16 family/TFAP2A/PSG9/TGF-β signaling pathway.
Yanlu XiongYangbo FengJinbo ZhaoJie LeiTianyun QiaoYongsheng ZhouQiang LuXiaofeng GuoLintao JiaYong HanPublished in: Cell death & disease (2021)
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).
Keyphrases
- epithelial mesenchymal transition
- transforming growth factor
- signaling pathway
- cell proliferation
- transcription factor
- long non coding rna
- lymph node metastasis
- poor prognosis
- long noncoding rna
- pi k akt
- squamous cell carcinoma
- induced apoptosis
- papillary thyroid
- genome wide
- young adults
- preterm birth
- anti inflammatory
- working memory
- rna seq
- squamous cell
- heat shock protein
- endoplasmic reticulum stress