Oncology Center, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
Department of Oncology, The First People's Hospital of Yunnan/Kunming University of Science and Technology Affiliated Hospital, Kunming, Yunnan 650032, P.R. China.
Mol Med Rep. 2018 Mar;17(3):4003-4010. doi: 10.3892/mmr.2017.8299. Epub 2017 Dec 18.
Gastric cancer is the fourth most common malignant disease and second leading cause of cancer‑associated mortalities worldwide. Previous studies revealed aberrantly expressed microRNAs (miRNAs) in various types of human cancer; these miRNAs play important roles in tumourigenesis and tumour development. miRNAs present a considerable potential for novel therapeutic approaches for treating human cancer. Therefore, the investigation of novel miRNAs involved in gastric cancer progression provides an opportunity to improve the prognosis of patients with gastric cancer. miRNA‑28 (miR‑28) has been investigated with regards to its expression and biological functions in many types of human cancer. However, previous studies have not discussed the expression patterns, roles and associated molecular mechanisms of miR‑28 in gastric cancer. In the present study, miR‑28 expression was identified to be upregulated in gastric cancer tissues and cell lines. miR‑28 inhibition functionally inhibited cell proliferation and invasion in gastric cancer in vitro. Using bioinformatics analysis, luciferase reporter assay, reverse transcription‑quantitative polymerase chain reaction and western blot analysis, phosphatase and tensin homolog (PTEN) was mechanically identified as a direct target of miR‑28 in gastric cancer. PTEN was downregulated in gastric cancer and negatively correlated with miR‑28 levels. Inhibition of PTEN restored the biological effects of miR‑28 downregulation on the proliferation and invasion of gastric cancer cells. Notably, the downregulation of miR‑28 results in the regulation of the phosphatidylinositol 3‑kinase/protein kinase B signaling pathway in gastric cancer. These results suggested that miR‑28 may be targeted for the development of novel treatments for gastric cancer in the future.
胃癌是全球第四大常见恶性肿瘤，也是癌症相关死亡的第二大主要原因。先前的研究表明，多种人类癌症中存在异常表达的 microRNAs（miRNAs）；这些 miRNAs 在肿瘤发生和肿瘤发展中发挥着重要作用。miRNAs 为治疗人类癌症提供了新的治疗方法的巨大潜力。因此，研究参与胃癌进展的新型 miRNAs 为改善胃癌患者的预后提供了机会。miR-28（miR-28）在多种人类癌症中的表达及其生物学功能已得到研究。然而，先前的研究尚未讨论 miR-28 在胃癌中的表达模式、作用和相关分子机制。在本研究中，鉴定到 miR-28 在胃癌组织和细胞系中呈上调表达。miR-28 抑制在体外功能性抑制胃癌细胞的增殖和侵袭。通过生物信息学分析、荧光素酶报告基因检测、逆转录-定量聚合酶链反应和 Western blot 分析，发现磷酸酶和张力蛋白同源物（PTEN）是 miR-28 在胃癌中的直接靶标。PTEN 在胃癌中下调，并与 miR-28 水平呈负相关。抑制 PTEN 恢复了 miR-28 下调对胃癌细胞增殖和侵袭的生物学效应。值得注意的是，miR-28 的下调导致了胃癌中磷脂酰肌醇 3-激酶/蛋白激酶 B 信号通路的调节。这些结果表明，miR-28 可能成为未来开发治疗胃癌新方法的靶点。
