Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
Clinical Laboratory, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
Int J Mol Med. 2019 Apr;43(4):1585-1596. doi: 10.3892/ijmm.2019.4083. Epub 2019 Jan 29.
MicroRNAs (miRNAs) have been shown to have a significant role in the progression of several types of cancer, including oral squamous cell carcinoma (OSCC). However, the biological function and regulatory mechanisms of miRNAs in OSCC remain to be fully elucidated. The aim of the present study was to investigate the role of miRNAs in OSCC and the relevant mechanism. Using a microarray, it was found that miRNA (miR)‑199a‑5p was one of the most downregulated miRNAs in OSCC tissues. A low expression of miR‑199a‑5p was closely associated with tumor differentiation, lymph node metastasis, tumor‑node‑metastasis stage, and overall survival rate. Functionally, the overexpression of miR‑199a‑5p suppressed cell proliferation, induced G0/G1 cell cycle arrest, and promoted the apoptosis of Tca8113 and SCC‑4 cells. Subsequently, inhibitor of nuclear factor‑κB (NF‑κB) kinase β (IKKβ), an important regulator of NF‑κB activation, was identified as a direct target of miR‑199‑5p. An inverse correlation was found between miR‑199a‑5p and IKKβ in tumor tissues. Further investigations revealed that the overexpression of IKKβ efficiently abrogated the influences caused by the overexpression of miR‑199a‑5p. It was also found that the miR‑199a‑5p‑mediated anticancer effects were dependent on the inhibition of NF‑κB activation. These findings indicate that miR‑199a‑5p functions as a tumor suppressor through regulation of the NF‑κB pathway by targeting IKKβ in OSCC.
微小 RNA(miRNAs)已被证明在多种癌症的进展中具有重要作用,包括口腔鳞状细胞癌(OSCC)。然而,miRNAs 在 OSCC 中的生物学功能和调控机制仍有待充分阐明。本研究旨在探讨 miRNAs 在 OSCC 中的作用及其相关机制。通过微阵列分析,发现 miRNA(miR)-199a-5p 是 OSCC 组织中下调最明显的 miRNA 之一。miR-199a-5p 的低表达与肿瘤分化、淋巴结转移、肿瘤-淋巴结-转移分期和总生存率密切相关。功能上,miR-199a-5p 的过表达抑制细胞增殖,诱导 G0/G1 细胞周期停滞,并促进 Tca8113 和 SCC-4 细胞凋亡。随后,核因子-κB(NF-κB)激活的重要调节因子核因子-κB 激酶β(IKKβ)被鉴定为 miR-199a-5p 的直接靶标。肿瘤组织中 miR-199a-5p 与 IKKβ 呈负相关。进一步研究表明,IKKβ 的过表达有效地消除了 miR-199a-5p 过表达所引起的影响。还发现 miR-199a-5p 介导的抗癌作用依赖于 NF-κB 激活的抑制。这些发现表明,miR-199a-5p 通过靶向 IKKβ 调节 NF-κB 通路,在 OSCC 中作为肿瘤抑制因子发挥作用。