Wang Haihua, Zhan Yuting, Peng Shuping, Fan Songqing, Wang Weiyuan
Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan, 410078, China.
J Cancer. 2022 Oct 24;13(14):3515-3525. doi: 10.7150/jca.77914. eCollection 2022.
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.
醛脱氢酶1A1（ALDH1A1）是醛脱氢酶家族中高度保守的同工酶之一。它主要参与细胞内醛类的代谢并形成转录调节因子，这对正常细胞的生长和分化至关重要。在许多恶性肿瘤和癌症干细胞（CSC）中，ALDH1A1的过表达与预后不良密切相关，并在传统癌症化疗期间促进肿瘤侵袭性和耐药性。在本研究中，我们发现ALDH1A1在乳腺癌（BRCA）、子宫颈癌（CESC）、肝癌（LIHC）、肺癌、肾细胞癌和胰腺癌（PAAD）中具有肿瘤抑制作用，但在皮肤黑色素瘤（SKCM）、多形性胶质母细胞瘤（GBM）、甲状腺癌（THCA）和膀胱癌（BLCA）中具有促肿瘤作用。至于鼻咽癌，ALDH1A1主要发挥致癌作用。我们发现，虽然ALDH1A1在鼻咽癌组织中的表达低于正常鼻咽黏膜组织，但在临床分期较高的患者中上调，且与患者预后不良相关。因此，我们通过获取GSE12452数据集进一步分析了ALDH1A1在鼻咽癌中的主要可能作用。基因集富集分析（GSEA）表明它可以抑制鼻咽癌细胞的坏死性凋亡。因此，我们使用靶向抑制剂NCT - 501，发现它可以抑制鼻咽癌细胞的增殖和干细胞球形成，并诱导坏死性凋亡。本研究探讨了ALDH1A1在各种肿瘤中的可能作用，并重点关注其作为鼻咽癌靶点的潜在作用。同时，ALDH1A1抑制剂在鼻咽癌中优先具有潜在治疗价值。
