Cai Qian, Yang Hsin-Sheng, Li Yi-Chen, Zhu Jiang
Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan, China.
Key Laboratory of Cardiovasular Proteomics of Shandong Province, Qilu Hospital of Shandong University, Jinan, China.
Front Oncol. 2022 Jun 20;12:855807. doi: 10.3389/fonc.2022.855807. eCollection 2022.
The human programmed cell death 4 () gene was mapped at chromosome 10q24 and encodes the PDCD4 protein comprised of 469 amino acids. PDCD4 inhibits protein translation PDCD4 inhibits protein translation to suppress tumor progression, and its expression is frequently decreased in breast cancer. PDCD4 blocks translation initiation complex by binding eIF4A MA-3 domains or by directly binding 5' mRNA internal ribosome entry sites with an RNA binding domain to suppress breast cancer progression and proliferation. Numerous regulators and biological processes including non-coding RNAs, proteasomes, estrogen, natural compounds and inflammation control PDCD4 expression in breast cancer. Loss of PDCD4 expression is also responsible for drug resistance in breast cancer. HER2 activation downregulates PDCD4 expression by activating MAPK, AKT, and miR-21 in aromatase inhibitor-resistant breast cancer cells. Moreover, modulating the microRNA/PDCD4 axis maybe an effective strategy for overcoming chemoresistance in breast cancer. Down-regulation of PDCD4 is significantly associated with short overall survival of patients, which suggests that PDCD4 may be an independent prognostic marker for breast cancer.
人类程序性细胞死亡4（）基因定位于10号染色体q24，编码由469个氨基酸组成的PDCD4蛋白。PDCD4抑制蛋白质翻译以抑制肿瘤进展，其表达在乳腺癌中经常降低。PDCD4通过结合eIF4A的MA-3结构域或通过用RNA结合结构域直接结合5' mRNA内部核糖体进入位点来阻断翻译起始复合物，从而抑制乳腺癌的进展和增殖。包括非编码RNA、蛋白酶体、雌激素、天然化合物和炎症在内的众多调节因子和生物学过程控制着乳腺癌中PDCD4的表达。PDCD4表达缺失也是乳腺癌耐药的原因。在芳香化酶抑制剂耐药的乳腺癌细胞中，HER2激活通过激活MAPK、AKT和miR-21来下调PDCD4表达。此外，调节微小RNA/PDCD4轴可能是克服乳腺癌化疗耐药的有效策略。PDCD4的下调与患者总体生存期短显著相关，这表明PDCD4可能是乳腺癌的一个独立预后标志物。
