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Keratin 6A gene silencing suppresses cell invasion and metastasis of nasopharyngeal carcinoma via the ??catenin cascade.

ABSTRACT: Nasopharyngeal carcinoma (NPC) is a type of head and neck cancer. This study aimed to study the mechanisms of ectopic keratin 6A (KRT6A) in NPC. Reverse transcription?quantitative polymerase chain reaction (RT?qPCR) and western blotting were performed to detect KRT6A levels in NPC cell lines (C666?1, 5?8F and SUNE?1) and a nasopharyngeal epithelial cell line (NP69, as a control). After SUNE?1 NPC cells had been silenced by KRT6A, cell viability, metastasis and invasion were determined using Cell Counting Kit?8, wound healing and Transwell assays, respectively. KRT6A levels, metastasis?associated factors and the Wnt/??catenin pathway were measured using RT?qPCR and western blotting. It was demonstrated that KRT6A was upregulated in all detected NPC cells, among which KRT6A was the highest in SUNE?1 cells. In SUNE?1 cells, cell viability was inhibited at 24 and 48 h, and that cell metastasis and invasion were demonstrated to be suppressed by KRT6A silencing. Both the mRNA and protein levels of KRT6A, matrix metalloproteinase (MMP)?2, MMP?9, ??catenin, lymphoid enhancer binding factor 1 and T?cell specific factor 4 were reduced in the small interfering (si)KRT6A group. However, the results demonstrated that the levels of epithelial?cadherin and tissue inhibitor of metalloproteinase?2 (TIMP?2) were promoted in the siKRT6A group. The activation of the Wnt/??catenin pathway by lithium chloride reversed the effect of si?KRT6A by modulating the expression of MMP?2/9 and TIMP2. It was observed that KRT6A silencing suppressed cell invasion and metastasis of NPC via the ??catenin cascade. Together these results provide important insights into a novel approach for the diagnosis and treatment of NPC.

SUBMITTER: Chen C

PROVIDER: S-EPMC6471251 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Keratin 6A gene silencing suppresses cell invasion and metastasis of nasopharyngeal carcinoma via the β‑catenin cascade.

Chen Chuanjun C Shan Huiguo H

Molecular medicine reports 20190318 5

Nasopharyngeal carcinoma (NPC) is a type of head and neck cancer. This study aimed to study the mechanisms of ectopic keratin 6A (KRT6A) in NPC. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blotting were performed to detect KRT6A levels in NPC cell lines (C666‑1, 5‑8F and SUNE‑1) and a nasopharyngeal epithelial cell line (NP69, as a control). After SUNE‑1 NPC cells had been silenced by KRT6A, cell viability, metastasis and invasion were determined using Cell ...[more]

PMID: 30896882

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Project description:BACKGROUND:The molecular mechanisms underlying dysregulation of microRNAs have been documented in nasopharyngeal carcinoma (NPC). Our previous study demonstrated that plasma miR-124 was down-regulated in NPC using microarray analysis and quantitative PCR validation. Though growing studies showed that down-regulated miR-124 was closely related to tumourigenesis in various types of cancers, the role of miR-124 in NPC remains largely unknown. METHODS:The expression level of miR-124 was evaluated in NPC cell lines and patient specimens using quantitative reverse transcription-PCR (Real-time qPCR). The clinicopathological significance of the resultant data was later analyzed. Then, we explored the role of miR-124 in NPC tumorigenesis by in vitro and in vivo experiments. Homo sapiens forkhead box Q1 (Foxq1) was confirmed as a novel direct target gene of miR-124 by the dual-luciferase assay and western bolt. RESULTS:We found that miR-124 was commonly down-regulated in NPC specimens and NPC cell lines. The expression of miR-124 was inversely correlation with clinical stages and marked on T stages. Then, the ectopic expression of miR-124 dramatically inhibited cell proliferation, colony formation, migration and invasion in vitro, as well as tumor growth and metastasis in vivo. Furthermore, we identified Foxq1 as a novel direct target of miR-124. Functional studies showed that knockdown of Foxq1 inhibited cell growth, migration and invasion, whereas Foxq1 overexpression partially rescued the suppressive effect of miR-124 in NPC. In clinical specimens, Foxq1 was commonly up-regulated in NPC, and the level increased with clinical stages and T stages. Additionally, the level of Foxq1 was inversely correlated with miR-124. CONCLUSIONS:Our results demonstrate that miR-124 functions as a tumor-suppressive microRNA in NPC, and that its suppressive effects are mediated chiefly by repressing Foxq1 expression. MiR-124 could serve as an independent biomarker to identify patients with different clinical characteristics. Therefore, our findings provide valuable clues toward the understanding the of mechanisms of NPC pathogenesis and provide an opportunity to develop new effective clinical therapies in the future.

Dataset Information

Keratin 6A gene silencing suppresses cell invasion and metastasis of nasopharyngeal carcinoma via the ??catenin cascade.

Publications

Keratin 6A gene silencing suppresses cell invasion and metastasis of nasopharyngeal carcinoma via the β‑catenin cascade.

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