Department of Colorectal and Anal Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Department of Burn Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Oncol Rep. 2021 Mar;45(3):1083-1093. doi: 10.3892/or.2020.7919. Epub 2020 Dec 31.
Long non‑coding RNAs play a role in a variety of malignancies, such as thyroid cancer (TC). However, the effects and function of lincRNA HOTAIRM1 (LINC HOTAIRM1) in TC remains obscure. In the present study, the expression of HOTAIRM1 was evaluated in TC tissues and cells by RT‑qPCR and the association between the lncRNA and disease progression was assessed. In vitro, the biological function of HOTAIRM1 was assessed in TC. Moreover, changes in the expression of Wnt10b were measured by western blot analysis. In addition, MTT assay, bioinformatics analysis and luciferase assays were performed to determine the target binding effect between LINC HOTAIRM1 and miR‑148a, as well as that between Wnt10b and miR‑148a. The changes in the metastatic ability of TPC‑1 and BCPAP cells were evaluated by Transwell assay. The pronounced upregulated expression of HOTAIRM1 was evident in TC cells and tissues, and was associated with TNM stage and lymph node metastasis. When HOTAIRM1 was knocked down, this inhibited the proliferative and invasive abilities of TPC‑1 and BCPAP cells in vitro. The knockdown of this lncRNA also increased the expression of microRNA‑148a (miR‑148a) and decreased Wnt10b expression in these cells, whereas transfection with miR‑148a inhibitor was sufficient to overcome this Wnt10b downregulation. In line with these results, the overexpression of miR‑148a markedly suppressed Wnt10b expression, whereas miR‑148a inhibition resulted in the opposite effects. The overexpression of Wnt10b was also sufficient to overcome the effects of miR‑148a mimics on TPC‑1 and BCPAP cells. Taken together, these results suggest that miR‑148a and Wnt10b are downstream effectors of the HOTAIRM1 signaling pathway in TC. This HOTAIRM1/miR‑148a/Wnt10 axis may thus be amenable to therapeutic targeting in order to improve disease outcomes in patients with TC.
长链非编码 RNA 在多种恶性肿瘤中发挥作用，如甲状腺癌 (TC)。然而，lncRNA HOTAIRM1（LINC HOTAIRM1）在 TC 中的作用和功能仍不清楚。在本研究中，通过 RT-qPCR 评估了 HOTAIRM1 在 TC 组织和细胞中的表达，并评估了该 lncRNA 与疾病进展的相关性。在体外，评估了 HOTAIRM1 在 TC 中的生物学功能。此外，通过 Western blot 分析测量了 Wnt10b 的表达变化。此外，进行了 MTT 测定、生物信息学分析和荧光素酶测定，以确定 LINC HOTAIRM1 与 miR-148a 之间以及 Wnt10b 与 miR-148a 之间的靶结合效应。通过 Transwell 测定评估了 TPC-1 和 BCPAP 细胞转移能力的变化。在 TC 细胞和组织中明显上调了 HOTAIRM1 的表达，并且与 TNM 分期和淋巴结转移有关。当敲低 HOTAIRM1 时，这抑制了 TPC-1 和 BCPAP 细胞在体外的增殖和侵袭能力。该 lncRNA 的敲低还增加了这些细胞中 microRNA-148a (miR-148a) 的表达并降低了 Wnt10b 的表达，而转染 miR-148a 抑制剂足以克服这种 Wnt10b 下调。与这些结果一致，miR-148a 的过表达显着抑制了 Wnt10b 的表达，而 miR-148a 的抑制则产生相反的效果。Wnt10b 的过表达也足以克服 miR-148a 模拟物对 TPC-1 和 BCPAP 细胞的影响。总之，这些结果表明，miR-148a 和 Wnt10b 是 TC 中 HOTAIRM1 信号通路的下游效应物。因此，HOTAIRM1/miR-148a/Wnt10 轴可能适合作为治疗靶点，以改善 TC 患者的疾病结局。
