Keratin 6A gene silencing suppresses cell invasion and metastasis of nasopharyngeal carcinoma via the β‑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/β-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, β-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/β-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 β-catenin cascade. Together these results provide important insights into a novel approach for the diagnosis and treatment of NPC.

Transcript levels of keratin 1/5/6/14/15/16/17 as potential prognostic indicators in melanoma patients

“…KRT6A and KRT6B both play important roles in the collective migration of keratinocytes 36 . Previous studies revealed that KRT6A silencing can suppress cell invasion and metastasis of nasopharyngeal carcinoma 37 . KRT6C was found to be closely related to the prognosis and metastasis of lung adenocarcinoma 38 .…”

Alteration of tumor-associated macrophage subtypes mediated by KRT6A in pancreatic ductal adenocarcinoma

“…By overlapping the DEGs between the M0-low group and the M0-high group in TCGA with the DEGs between ANT and PDAC, we acquired the potential regulatory genes of TAMs, IAPP, and KRT6A. KRT6A is related to cell invasion and metastasis of nasopharyngeal carcinoma via the β-catenin cascade [ 36 ]. The KRT6A-positive subset of mammary epithelial cells can be induced to form cancer by ErbB2 [ 37 ].…”

KRT6A Promotes EMT and Cancer Stem Cell Transformation in Lung Adenocarcinoma

“…A nontargeting small interfering RNA (siRNA) 5 0 -CCTAAGGTTAAGTCGCC CTCGCTC-3 0 was used as a negative control, for KRT6A siRNA knockdown experiments the si-RNA targeting sequence, 5 0 -CCAGCAGGAAGAGCUAUA-3 0 was introduced. 6 Transfection efficiency was evaluated by using quantitative reverse transcription PCR (qRT-PCR) and Western blot 48 hours after transfection.…”

“…13, which encodes the cytokeratin 6A protein. Keratin 6A is a family member of type II keratin proteins, biologically KRT6A could lead to epidermalization of squamous epithelium, 6,7 and KRT6A plays an important role in EMT in nasopharyngeal carcinoma, 6 KRT6A mutation plays an important role in pachyonychia congenita and could serve as a diagnosis marker. [7][8][9] In present study, the in vitro KRT6A silencing model was constructed to investigate the biological role of KRT6A.…”