Jin Hui-Fang, Wang Ju-Feng, Song Ting-Ting, Zhang Jun, Wang Lin
Department of Blood Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Oncology, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.
Front Oncol. 2020 May 6;10:643. doi: 10.3389/fonc.2020.00643. eCollection 2020.
Downregulation of microRNA-200b (miR-200b) has been identified in a range of cancers, yet the specific mechanisms whereby it influences lung cancer growth require further exploration. We determined that lung cancer patient tumor samples exhibit decreased miR-200b expression, and we further found this miRNA to inhibit tumor growth via interfering with ERK1/2 and AKT signaling, targeting p70S6K1 to suppress HIF-1α expression. This miRNA further rendered H1299 cells more sensitive to cisplatin while impairing their proliferative and invasive potential through its ability to target and inhibit the activity of p70S6K1. These results were further confirmed in a murine xenograft model in which miR-200b also inhibited the growth of tumor and suppressed p70S6K1, p-AKT, p-ERK1/2, and HIF-1α expression. These findings clearly demonstrate a role for miR-200b in suppressing lung cancer development, making it a potentially relevant target for future diagnostic and therapeutic interventions.
在多种癌症中已发现微小RNA-200b（miR-200b）表达下调，但其影响肺癌生长的具体机制仍需进一步探索。我们发现肺癌患者的肿瘤样本中miR-200b表达降低，并且进一步发现该微小RNA通过干扰ERK1/2和AKT信号通路，靶向p70S6K1以抑制HIF-1α表达，从而抑制肿瘤生长。该微小RNA还使H1299细胞对顺铂更敏感，同时通过其靶向并抑制p70S6K1活性的能力损害其增殖和侵袭潜能。这些结果在小鼠异种移植模型中得到进一步证实，在该模型中miR-200b也抑制肿瘤生长并抑制p70S6K1、p-AKT、p-ERK1/2和HIF-1α的表达。这些发现清楚地证明了miR-200b在抑制肺癌发展中的作用，使其成为未来诊断和治疗干预的潜在相关靶点。
