» Articles » PMID: 30720059

MicroRNA‑199a‑5p Functions As a Tumor Suppressor in Oral Squamous Cell Carcinoma Via Targeting the IKKβ/NF‑κB Signaling Pathway

Overview
Journal Int J Mol Med
Specialty Genetics
Date 2019 Feb 6
PMID 30720059
Citations 21
Authors
Affiliations
Soon will be listed here.
Abstract

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.

Citing Articles

The miR-199a-5p/HIF1α dual-regulatory axis participates in hypoxia-induced aggressive phenotypes of oral squamous cell carcinoma (OSCC) cells.

Chen X, Yu J, Tian H, Cai X Int J Clin Oncol. 2024; 29(9):1244-1254.

PMID: 38853186 DOI: 10.1007/s10147-024-02555-7.


MiR-199a-5p-Regulated SMARCA4 Promotes Oral Squamous Cell Carcinoma Tumorigenesis.

Xu M, Zhang J, Lu X, Liu F, Shi S, Deng X Int J Mol Sci. 2023; 24(5).

PMID: 36902184 PMC: 10003091. DOI: 10.3390/ijms24054756.


Research progress and clinical application prospects of miRNAs in oral cancer.

Xing L, Feng Z, Nie H, Liu M, Liu Y, Zhang X Mol Biol Rep. 2022; 49(11):10653-10665.

PMID: 35725854 DOI: 10.1007/s11033-022-07604-w.


Clinicopathological analysis and prognostic significance of NF-κB p65 and IKKβ protein and mRNA expression in nasopharyngeal carcinoma.

Zhou M, Zhao G, Zhou X, Xuan R, Chen Y, Wang Y J Int Med Res. 2022; 50(1):3000605211069195.

PMID: 34994235 PMC: 8743962. DOI: 10.1177/03000605211069195.


Identification of and Target Genes: Paxillin Facilities Cancer Cell Aggressiveness in Head and Neck Squamous Cell Carcinoma.

Tanaka N, Minemura C, Asai S, Kikkawa N, Kinoshita T, Oshima S Genes (Basel). 2021; 12(12).

PMID: 34946859 PMC: 8701835. DOI: 10.3390/genes12121910.


References
1.
Pan M, Lin-Shiau S, Lin J . Comparative studies on the suppression of nitric oxide synthase by curcumin and its hydrogenated metabolites through down-regulation of IkappaB kinase and NFkappaB activation in macrophages. Biochem Pharmacol. 2000; 60(11):1665-76. DOI: 10.1016/s0006-2952(00)00489-5. View

2.
Shen Q, Cicinnati V, Zhang X, Iacob S, Weber F, Sotiropoulos G . Role of microRNA-199a-5p and discoidin domain receptor 1 in human hepatocellular carcinoma invasion. Mol Cancer. 2010; 9:227. PMC: 2939569. DOI: 10.1186/1476-4598-9-227. View

3.
Jiang J, Gusev Y, Aderca I, Mettler T, Nagorney D, Brackett D . Association of MicroRNA expression in hepatocellular carcinomas with hepatitis infection, cirrhosis, and patient survival. Clin Cancer Res. 2008; 14(2):419-27. PMC: 2755230. DOI: 10.1158/1078-0432.CCR-07-0523. View

4.
Nakayama H, Ikebe T, Beppu M, Shirasuna K . High expression levels of nuclear factor kappaB, IkappaB kinase alpha and Akt kinase in squamous cell carcinoma of the oral cavity. Cancer. 2001; 92(12):3037-44. DOI: 10.1002/1097-0142(20011215)92:12<3037::aid-cncr10171>3.0.co;2-#. View

5.
Huang L, Lin J, Yu Y, Zhang M, Wang H, Zheng M . Downregulation of six microRNAs is associated with advanced stage, lymph node metastasis and poor prognosis in small cell carcinoma of the cervix. PLoS One. 2012; 7(3):e33762. PMC: 3306296. DOI: 10.1371/journal.pone.0033762. View