Role of the MALAT1-Importin 7-HIF1A regulatory axis in the progression of cutaneous squamous cell carcinoma.

Ultraviolet-B radiation is a major environmental factor contributing to the development of cutaneous squamous cell carcinoma (cSCC). In our previous study, we found that UVB exposure induces the expression of the long non-coding RNA (lncRNA) MALAT1 in HaCaT cells, and that MALAT1 promotes cSCC progression. In the present study, we observed that MALAT1 regulates the expression of the nuclear transporter protein Importin 7 (IPO7) in human cSCC. Both in vitro and in vivo experiments showed that IPO7 plays a pro-tumorigenic role in cSCC by promoting cell proliferation, migration, and invasion, and by inhibiting apoptosis. Furthermore, an interaction between IPO7 and HIF1α (HIF1A) was identified; silencing IPO7 impaired the nuclear import of HIF1α and reduced its transcriptional activity. Mechanistically, we found that MALAT1 co-binds with the transcription factor c-MYC at the IPO7 promoter to regulate IPO7 expression. Collectively, our data suggest that the MALAT1-IPO7-HIF1α axis may promote the malignant behaviors of cSCC cells and contribute to cSCC progression.