CD95 promotes stemness of colorectal cancer cells by lncRNA MALAT1
CD95 promotes stemness of colorectal cancer cells by lncRNA MALAT1
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DOI：
10.1016/j.lfs.2023.122394
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发表时间：
2024-01-06
期刊：
影响因子：
6.1
通讯作者：
Chen，Zhigang
中科院分区：
文献类型：
--
作者：
Gao，Chenyi;Jia，Kunpeng;Chen，Zhigang
结直肠癌（CRC）是第二大致死性癌症。许多研究表明，癌症的干性导致对常规化疗的抵抗和不良预后。然而，在CRC中维持癌症干性的机制仍然不清楚，并且很少有临床药物用于靶向癌症干性。先前的研究已经报道了CD95在外源性激动剂CD95配体（CD95L）的长期刺激下增加癌细胞的干细胞性。然而，CD95L在某些人类肿瘤组织中的表达相对较低。本研究发现CD95在大肠癌细胞中高表达，在体外不受外源性CD95L刺激的情况下，CD95可促进肿瘤球形成、化疗耐药和体内肿瘤生长。整体和单细胞RNA测序结果表明，CD95通过上调长链非编码RNA转移相关肺腺癌转录物1（lncRNAMALAT1）促进CRC细胞的干细胞性，MALAT1敲低抑制CD95诱导的肿瘤球形成和化疗耐药性。总之，我们的研究结果表明，CD95具有通过lncRNAMALAT1的作用调节癌症干性的能力。靶向CD95可能是抑制CRC中癌症干细胞的有希望的策略。
Colorectal cancer (CRC) is the second most fatal cancer. Many studies have shown that cancer stemness contributes to resistance to conventional chemotherapy and poor prognosis. However, the mechanisms involved in maintaining cancer stemness in CRC are still obscure and few clinical drugs were used to target cancer stemness. Previous studies had reported CD95 increases the stemness of cancer cells with long-term stimulation of exogenous agonist CD95 ligand (CD95L). However, the expression of CD95L is relative low in certain human tumor tissues. In this study, we found that CD95 was highly expressed in CRC cells, and in vitro it promoted the tumorsphere formation, chemotherapy resistance and in vivo tumor growth without stimulation of exogenous CD95L. Mechanistically, the bulk and single-cell RNA-sequencing results suggested that CD95 promotes stemness of CRC cells through upregulation of long non-coding RNAs metastasis-associated lung adenocarcinoma transcript 1 (lncRNAMALAT1).MALAT1knockdown inhibited CD95-induced tumorsphere formation and chemotherapy resistance. In summary, our findings reveal that CD95 has the capability to modulate cancer stemness via the action of the lncRNAMALAT1. Targeting CD95 may be a promising strategy to inhibit cancer stemness in CRC.