MicroRNA‑199a‑5p functions as a tumor suppressor in oral squamous cell carcinoma via targeting the IKKβ/NF‑κB signaling pathway
| Autor: | Xiaodong Yang, Yanjun Zhou, Dongyi Wei, Weixin Wang, Yuebao Shao, Baohong Shen, Guangjian Lu, Jianbin Yang |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Cell Survival microRNA-199a-5p Cell Down-Regulation Apoptosis Biology Models Biological nuclear factor-κB activation 03 medical and health sciences 0302 clinical medicine Cell Line Tumor microRNA Genetics medicine Humans Genes Tumor Suppressor Cell Proliferation Oncogene Base Sequence Cell growth Cell Cycle inhibitor of nuclear factor-κβ kinase NF-kappa B General Medicine Cell Cycle Checkpoints Articles Cell cycle Middle Aged Molecular medicine I-kappa B Kinase Gene Expression Regulation Neoplastic oral squamous cell carcinoma stomatognathic diseases MicroRNAs 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer research Carcinoma Squamous Cell Female Mouth Neoplasms Signal transduction G1 phase Signal Transduction |
| Zdroj: | International Journal of Molecular Medicine |
| ISSN: | 1791-244X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|