Mechanism of lncRNA FEZF1-AS1 in promoting the occurrence and development of oral squamous cell carcinoma through targeting miR-196a

OBJECTIVE: Previous studies have demonstrated that long non-coding ribonucleic acid (lncRNA) FEZF1-AS1 acts as a cancer-promoting gene. However, no reports have investigated the role of FEZF1-AS1 in oral squamous cell carcinoma (OSCC) yet. Therefore, the aim of this study was to explore whether FEZF1-AS1 promoted the expression characteristics of OSCC by targeting miR-196a and to further elucidate the underlying mechanism of FEZF1-AS1 in promoting the metastasis of OSCC.

PATIENTS AND METHODS: The expression levels of FEZF1-AS1 and miR-196a in 42 pairs of OSCC tissues and para-carcinoma tissues were detected via quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation of FEZF1-AS1 expression with clinical indexes and prognosis of OSCC patients was analyzed. Moreover, the expression levels of FEZF1-AS1 and miR-196a in OSCC cells were detected via qRT-PCR. FEZF1-AS1 knockdown and miR-196a over-expression models were established using lentivirus transfection in OSCC cell lines (CAL-27 and Tca8113). Subsequently, the influences of FEZF1-AS1 and miR-196a on the biological functions of OSCC cells were analyzed via Cell Counting Kit-8 (CCK-8) assay, colony formation assay and 5-Ethynyl-2'-deoxyuridine (EdU) assay, respectively. Furthermore, the potential mechanism was explored using the Luciferase reporter gene and recovery assays.

RESULTS: The results of qRT-PCR proved that the expression level of FEZF1-AS1 in OSCC tissues was significantly higher than that of para-carcinoma tissues, and the difference was statistically significant. The pathological stage was significantly higher in patients with high-expression FEZF1-AS1 than those with low-expression FEZF1-AS1, while the overall survival rate was remarkably lower. The proliferation ability of cells in FEZF1-AS1 silencing group declined significantly when compared with the NC group. Similarly, qRT-PCR results verified that the expression of miR-196a in OSCC cell lines and tissues was significantly reduced as well. Meanwhile, the miR-196a expression was negatively correlated with FEZF1-AS1. Subsequent Luciferase reporter gene assay confirmed that overexpression of miR-196a could markedly reduce the activity of Luciferase containing wild-type FEZF1-AS1 vector rather than decrease the activity of Luciferase containing mutant-type vector or empty vector. These findings further indicated that FEZF1-AS1 could be targeted by miR-196a through this binding site. In addition, recovery assay demonstrates that there was a mutual regulatory effect between FEZF1-AS1 and miR-196a, jointly affecting the malignant progression of OSCC.

CONCLUSIONS: The expression of lncRNA FEZF1-AS1 was markedly up-regulated in OSCC, which was significantly correlated with pathological stage and poor prognosis of OSCC patients. Therefore, it was believed that FEZF1-AS1 might promote the malignant progression of OSCC by regulating miR-196a.

Medienart:

E-Artikel

Erscheinungsjahr:

2019

Erschienen:

2019

Enthalten in:

Zur Gesamtaufnahme - volume:23

Enthalten in:

European review for medical and pharmacological sciences - 23(2019), 15 vom: 05. Aug., Seite 6505-6515

Sprache:

Englisch

Beteiligte Personen:

Xu, L [VerfasserIn]
Hou, T-J [VerfasserIn]
Yang, P [VerfasserIn]

Links:

Volltext

Themen:

FEZF1 protein, human
Journal Article
MIRN196 microRNA, human
MicroRNAs
RNA, Long Noncoding
Repressor Proteins

Anmerkungen:

Date Completed 02.10.2020

Date Revised 02.10.2020

published: Print

Citation Status MEDLINE

doi:

10.26355/eurrev_201908_18534

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM299901688