Department of Respiration, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, P.R. China.
Int J Oncol. 2019 Mar;54(3):929-941. doi: 10.3892/ijo.2019.4695. Epub 2019 Jan 24.
Considering the joint contribution of long non‑coding RNAs (lncRNAs) and microRNAs (miRNAs/miRs) to tumorigenesis, the aim of the present study was to investigate whether and how lncRNA H19 targets miR‑29b‑3p to affect the progression of lung adenocarcinoma by the modulation of signal transducer and activator of transcription 3 (STAT3). A total of 305 lung adenocarcinoma tissues and four human lung adenocarcinoma cell lines (i.e. Calu‑3, NCI‑H1975, A549 and NCI‑H23) were used. pcDNA3.1‑H19, short interfering RNA (si‑)H19, miR‑29b‑3p mimic, miR‑29b‑3p inhibitor and negative control (NC) were transfected into the cells, and the proliferation, viability and apoptosis of the cells were determined using a Cell Counting Kit‑8 assay, colony formation assay and flow cytometry, respectively. The results indicated that highly expressed H19 and poorly expressed miR‑29b‑3p could serve as predictors for the poor prognosis of lung adenocarcinoma patients. Additionally, si‑H19 and miR‑29b‑3p mimic significantly increased the apoptosis of lung adenocarcinoma cells, and decreased the survival rate and viability of cells. Simultaneously, expression of epithelial‑mesenchymal transition (EMT)‑specific proteins was significantly altered, i.e. increased epithelial cadherin expression, as well as decreased vimentin, Snail and Slug expression. Furthermore, miR‑29b‑3p was verified to be targeted and regulated by H19, and STAT3 was targeted and modified by miR‑29b‑3p. Ultimately, STAT3 was identified to decrease lung adenocarcinoma cell viability, survival, apoptosis and EMT imposed by miR‑29b‑3p. In conclusion, the results of the present study indicated that lncRNA H19/miR‑29b‑3p/STAT3 signaling was involved in the development of lung adenocarcinoma, which may be critical for developing effective diagnostic and treatment strategies for lung adenocarcinoma.
考虑到长非编码 RNA（lncRNA）和 microRNA（miRNA/miRs）共同促进肿瘤发生，本研究旨在探讨 lncRNA H19 是否以及如何通过调节信号转导和转录激活因子 3（STAT3）来靶向 miR-29b-3p 影响肺腺癌的进展。共使用了 305 例肺腺癌组织和 4 个人肺腺癌细胞系（即 Calu-3、NCI-H1975、A549 和 NCI-H23）。将 pcDNA3.1-H19、短发夹 RNA（si）-H19、miR-29b-3p 模拟物、miR-29b-3p 抑制剂和阴性对照（NC）转染到细胞中，分别使用细胞计数试剂盒-8 测定、集落形成测定和流式细胞术来测定细胞的增殖、活力和凋亡。结果表明，高表达的 H19 和低表达的 miR-29b-3p 可作为肺腺癌患者预后不良的预测指标。此外，si-H19 和 miR-29b-3p 模拟物显著增加了肺腺癌细胞的凋亡，降低了细胞的存活率和活力。同时，上皮-间充质转化（EMT）特异性蛋白的表达也发生了显著改变，即上皮钙黏蛋白表达增加，而波形蛋白、Snail 和 Slug 表达减少。此外，miR-29b-3p 被证实是 H19 的靶标和调节物，而 STAT3 是 miR-29b-3p 的靶标和修饰物。最终，STAT3 被鉴定为降低 miR-29b-3p 诱导的肺腺癌细胞活力、存活、凋亡和 EMT。综上所述，本研究结果表明，lncRNA H19/miR-29b-3p/STAT3 信号参与了肺腺癌的发生发展，这对于开发肺腺癌有效的诊断和治疗策略可能具有重要意义。
