BHLHE40, a potential immune therapy target, regulated by FGD5-AS1/miR-15a-5p in pancreatic cancer.
BHLHE40, a potential immune therapy target, regulated by FGD5-AS1/miR-15a-5p in pancreatic cancer.
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DOI：
10.1038/s41598-023-43577-x
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发表时间：
2023-09-29
影响因子：
4.6
通讯作者：
Liu, Yihao
中科院分区：
文献类型：
--
作者：
Qi, Wenxin;Liu, Qian;Fu, Wenjun;Shi, Jiaming;Shi, Minmin;Duan, Songqi;Li, Zhe;Song, Shaohua;Wang, Jiao;Liu, Yihao
胰腺癌作为恶性程度最高的肿瘤之一，近年来已成为人们关注的主要疾病。BHLHE 40是一种重塑肿瘤免疫微环境的关键转录因子，已被描述为在多种肿瘤相关免疫细胞中显著增加。然而，BHLHE 40对胰腺癌的促癌生物学功能和潜在的分子机制及其独特的微环境尚不清楚。因此，我们通过生物信息学分析和细胞生物学实验研究了BHLHE 40在胰腺癌微环境中的促癌作用，并确定BHLHE 40在胰腺癌组织中的表达明显高于癌旁正常组织。同时，Kaplan-Meier生存分析显示，BHLHE 40的低表达与患者的预后良好密切相关。受试者工作特征（ROC）曲线分析证实了BHLHE 40相关预测模型的准确性。斯皮尔曼相关分析发现BHLHE 40的高表达可能与胰腺癌的免疫抑制有关。BHLHE 40基因的沉默可以抑制胰腺癌细胞的增殖、侵袭和凋亡，有望成为胰腺癌潜在的治疗靶点。此外，我们探索并验证了FGD 5-AS 1/miR-15 a-5 p轴作为胰腺癌中BHLHE 40高表达的潜在上游调控模式。综上所述，我们的数据表明，参与调节BHLHE 40的ceRNA有助于促进胰腺的免疫抑制反应，并有望成为胰腺癌的诊断标志物和潜在的免疫靶点。
Pancreatic cancer, as one of the neoplasms with the highest degree of malignancy, has become a main disease of concerns in recent years. BHLHE40, a critical transcription factor for remodeling of the tumor immune microenvironment, has been described to be substantially increased in a variety of tumor-associated immune cells. Nevertheless, the pro-cancer biological functions and underlying molecular mechanisms of BHLHE40 for pancreatic cancer and its unique microenvironment are unclear. Hereby, we investigated the pro-oncogenic role of BHLHE40 in the pancreatic cancer microenvironment by bioinformatics analysis and cell biology experiments and determined that the expression of BHLHE40 was obviously elevated in pancreatic cancer tissues than in adjacent normal tissues. In parallel, Kaplan–Meier survival analysis unveiled that lower expression of BHLHE40 was strongly associated with better prognosis of patients. Receiver operating characteristic (ROC) curve analysis confirmed the accuracy of the BHLHE40-related prediction model. Subsequent, spearman correlation analysis observed that higher expression of BHLHE40 might be involved in immunosuppression of pancreatic cancer. Silencing of BHLHE40 could inhibit proliferation, invasion, and apoptosis of pancreatic cancer in vitro and in vivo, implying that BHLHE40 is expected to be a potential therapeutic target for pancreatic cancer. In addition, we explored and validated the FGD5-AS1/miR-15a-5p axis as a potential upstream regulatory mode for high expression of BHLHE40 in pancreatic cancer. In summary, our data showed that ceRNA involved in the regulation of BHLHE40 contributes to the promotion of immunosuppressive response in pancreatic and is expected to be a diagnostic marker and potential immunotherapeutic target for pancreatic cancer.
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影响因子：
4.3
作者：
Johansson H;Andersson R;Bauden M;Hammes S;Holdenrieder S;Ansari D
通讯作者：
Ansari D
DOI：
10.1038/s41575-021-00457-x
发表时间：
2021-07
期刊：
Nature reviews. Gastroenterology & hepatology
影响因子：
--
作者：
通讯作者：
--
影响因子：
9
作者：
Quan, Gang;Xu, Jian;Wang, Jie;Liu, Xinyuan;Xu, Jichuan;Jiang, Jianxin
通讯作者：
Jiang, Jianxin
影响因子：
5.5
作者：
Ghafouri-Fard S;Fathi M;Zhai T;Taheri M;Dong P
通讯作者：
Dong P
胰腺癌的联合治疗：基于抗 PD-(L)1 的策略
DOI：
10.1186/s13046-022-02273-w
发表时间：
2022-02-09
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Liu L;Huang X;Shi F;Song J;Guo C;Yang J;Liang T;Bai X
通讯作者：
Bai X