Shanxi Tumour Hospital; Department of respiration, Shanxi Tumour Hospital, Taiyuan 030013, Shanxi Province, China.
the First Affiliated Hospital of Anhui Medical University; Medical Oncology, the First Affiliated Hospital of Anhui Medical University; Hefei 230022, Anhui Province, China.
Front Biosci (Landmark Ed). 2020 Mar 1;25(5):948-960. doi: 10.2741/4842.
Long noncoding RNA prostate cancer-associated transcript 1 (PCAT1) is oncogenic and causes progression of non-small cell lung cancer (NSCLC). We hypothesized that PCAT1 might be involved in the acquisition of chemoresistance of NSCLC cells to treatment with cisplatin (DDP). Here, we show that PCAT1 and ATP-binding cassette sub-family B member 1 (ABCB1) are highly expressed in NSCLC tissues and cell lines, and regulate the growth and apoptosis of these cells. Compared with those in DDP-sensitive patients, PCAT1 and ABCB1 are highly expressed in the tumors of DDP-resistant patients, and such overexpression correlates with a shorter overall survival of these patients. Knockdown of PCAT1 or upregulation of miR-129 led to apoptosis and sensitized the DDP-resistant cells to DDP. The 3' UTR activity of PCAT1 and ABCB1, which was increased by PCAT1 overexpression, was shown to harbor an miR-129 binding site. DDP resistance is induced by elevated ABCB1 expression, which involves binding of miR-129 in DDP resistant cells. These findings suggest that the PCAT1/miR-129/ABCB1 axis may be a potential target for the treatment of DDP-resistant oat cell cancer.
长链非编码 RNA 前列腺癌相关转录本 1（PCAT1）是致癌的，导致非小细胞肺癌（NSCLC）的进展。我们假设 PCAT1 可能参与 NSCLC 细胞对顺铂（DDP）治疗的获得性耐药。在这里，我们表明 PCAT1 和 ABCB1 亚家族 B 成员 1（ABCB1）在 NSCLC 组织和细胞系中高度表达，并调节这些细胞的生长和凋亡。与 DDP 敏感患者相比，DDP 耐药患者的肿瘤中 PCAT1 和 ABCB1 表达水平较高，这种过表达与这些患者的总生存期较短相关。PCAT1 的敲低或 miR-129 的上调导致 DDP 耐药细胞凋亡，并使这些细胞对 DDP 敏感。由 PCAT1 过表达引起的 PCAT1 和 ABCB1 的 3'UTR 活性被证明含有 miR-129 结合位点。ABCB1 表达的升高诱导 DDP 耐药，这涉及 miR-129 在 DDP 耐药细胞中的结合。这些发现表明，PCAT1/miR-129/ABCB1 轴可能是治疗 DDP 耐药燕麦细胞癌的潜在靶点。
