Department of Thoracic surgery, The Second Affiliated Hospital of Kunming Medical University, 650101, Kunming, Yunnan, China.
Mailman School of Public Health, Columbia University, New York, USA.
J Mol Histol. 2021 Jun;52(3):503-510. doi: 10.1007/s10735-020-09943-z. Epub 2021 Jan 29.
Rhomboid domain containing 1 (RHBDD1) gene, which was reported to be upregulated in human several cancer, was associated with carcinogenesis. However, the potential biological function of RHBDD1 in non-small cell lung cancer (NSCLC) carcinogenesis remains still not known. In this study, we aimed to investigate the role of RHBDD1 and its underlying molecular mechanism in NSCLC. The gene RHBDD1 expression was detected in NSCLC tissues and matched nontumor adjacent tissues. In vitro experiments, NSCLC cell lines (A549, H1650, H358 and H1299) were performed to investigate the biological function of RHBDD1 and its molecular mechanism. Our findings showed that the mRNA and protein expression levels of RHBDD1 were notably increased in human NSCLC tissues and cell lines, especially in A549 and H1650 cells. Moreover, silencing of RHBDD1 by RNAi notably inhibited NSCLC cell proliferation and increased cell apoptosis. Caspase-3/7 activity was remarkably increased in cells treated with RHBDD1 siRNA. RHBDD1 silencing notably reduced the number of invading cells. Furthermore, our findings showed that silencing of RHBDD1 notably inhibited the mRNA and protein expression levels of ZEB1 in A549 and H1650 cells. The phosphorylation of PI3K and AKT was also remarkably decreased by RHBDD1 silencing. ZEB1/AKT overexpression reversed the effect of RHBDD1 silencing on NSCLC cell growth and invasion. Taken together, our findings indicated that RHBDD1 silencing inhibited cell growth and invasion of non-small cell lung cancer by mediating ZEB1/PI3K/AKT signaling pathway, implying that RHBDD1 was possibly a potential diagnostic and therapeutic target for NSCLC treatment.
菱形结构域包含 1 型（RHBDD1）基因在多种人类癌症中呈上调表达，与致癌作用有关。然而，RHBDD1 在非小细胞肺癌（NSCLC）发生中的潜在生物学功能仍然未知。在这项研究中，我们旨在研究 RHBDD1及其在 NSCLC 发生中的潜在分子机制。检测了 NSCLC 组织和配对的非肿瘤相邻组织中的 RHBDD1 基因表达。在体外实验中，研究了 RHBDD1 在 NSCLC 细胞系（A549、H1650、H358 和 H1299）中的生物学功能及其分子机制。研究结果表明，RHBDD1 的 mRNA 和蛋白表达水平在人 NSCLC 组织和细胞系中明显升高，尤其是在 A549 和 H1650 细胞中。此外，通过 RNAi 沉默 RHBDD1 显著抑制 NSCLC 细胞增殖并增加细胞凋亡。用 RHBDD1 siRNA 处理的细胞中 caspase-3/7 活性明显增加。RHBDD1 沉默显著减少了侵袭细胞的数量。此外，研究结果表明，沉默 RHBDD1 显著降低了 A549 和 H1650 细胞中 ZEB1 的 mRNA 和蛋白表达水平。PI3K 和 AKT 的磷酸化也因 RHBDD1 沉默而明显降低。ZEB1/AKT 的过表达逆转了 RHBDD1 沉默对 NSCLC 细胞生长和侵袭的影响。总之，我们的研究结果表明，RHBDD1 沉默通过调节 ZEB1/PI3K/AKT 信号通路抑制非小细胞肺癌细胞的生长和侵袭，这表明 RHBDD1 可能是 NSCLC 治疗的潜在诊断和治疗靶点。
