Targeting ALDH1A1 to induce Necroptosis in Nasopharyngeal Carcinoma

ALDH1A1 is one of the highly conserved isoenzymes of the aldehyde dehydrogenase family. It is mainly involved in the metabolism of intracellular aldehydes and forms transcriptional regulators, which are essential for growth and differentiation of normal cells. Overexpression of ALDH1A1 in many malignancies and cancer stem cells (CSCs) is closely associated with poor prognosis and promotes tumor aggressiveness and drug resistance during conventional cancer chemotherapy. In this study, we found that ALDH1A1 had tumor suppressor effects in BRCA, CESC, LIHC, Lung cancer, renal cell carcinoma and PAAD, but tumor-promoting effects in SKCM, GBM, THCA and BLCA. As for the nasopharyngeal carcinoma, ALDH1A1 mainly played a carcinogenic role. We found that although the expression of ALDH1A1 in NPC tissue was lower than that in normal nasopharyngeal mucosal tissue, it was upregulated in patients with higher clinical stages, and correlated with poor patient outcomes. Therefore, we further analyzed the main possible role of ALDH1A1 in NPC by taking GSE12452 dataset. The GSEA enrichment analysis showed that it could inhibit the necroptosis of nasopharyngeal carcinoma cells. Therefore, we used the targeted inhibitor NCT-501 and found that it could inhibit the proliferation and stem cell spheroidization of NPC cells, and induce necroptosis. This study explored the possible role of ALDH1A1 in various tumors and focused on its potential role as a target in NPC. Meanwhile, ALDH1A1 inhibitor preferentially has potential therapeutic value in NPC.