KRT4 suppresses oral squamous cell carcinoma development by reducing ATG4B-mediated autophagy

Abstract

Head and neck squamous cell carcinoma is the sixth most common tumor worldwide, and half of head and neck squamous cell carcinoma patients are with oral squamous cell carcinoma (OSCC). 300,000 new cases of OSCC were reported annually. Even with multi-modality treatment, the prognosis of OSCC remains unsatisfactory. Thus, it is urgent to discover novel therapeutic targets for OSCC. Some microarray studies have revealed that Keratin 4 (KRT4) is downregulated in OSCC, whereas its role in OSCC development remains unknown. The present study revealed that KRT4 suppressed OSCC progression by inducing cell apoptosis and inhibiting cell invasion. In addition, KRT4 over-expression inhibited autophagy by blocking the interaction of autophagy-related 4B cysteine peptidase (ATG4B) and microtubule-associated protein 1A/1B light chain 3 (LC3) to regulate apoptosis and invasion of OSCC.In conclusion, KRT4 played an important role in OSCC development through regulating ATG4B-mediated autophagy and may be a novel therapeutic drug target of OSCC.

Splice site m6A methylation prevents binding of DGCR8 to suppress KRT4 pre-mRNA splicing in oral squamous cell carcinoma

“…Normal oral keratinocytes (NOK) and OSCC cell line HN6 cells were obtained from Cell Bank at the Chinese Academy of Sciences (Shanghai, China) and cultured as previously described ( Li et al, 2022 ).…”

“…Cells were transfected with METTL3, METTL14 or DGCR8 siRNA and siRNA negative control (NC) by Lipofectamine 2000 (Invitrogen, Carlsbad, CA, USA) as previously described ( Li et al, 2022 ). Then cells were collected for following experiments at 48 h after transfection.…”

“…After RNA extraction and cDNA synthesis, qRT-PCR was performed by the ABI7300 Real-Time PCR system (Applied Biosystems, Foster City, CA, USA) using TB Green ® Premix Ex Taq™ II (Tli RNaseH Plus) (Takara) as previously described ( Li et al, 2022 ). Sequences of primers used for qRT-PCR were listed in Table 3 .…”

“…Quantitative data of the current study were present as mean ± standard deviation (SD) and statistical differences were analyzed by SPSS 20 software (SPSS Inc., Chicago, IL, USA) as previously described ( Li et al, 2022 ). Besides, P < 0.05 was considered as statistically significant.…”

“…Previous studies have indicated that KRT4 expression is downregulated in OSCC ( Lallemant et al, 2009 ; Toruner et al, 2004 ; Ye et al, 2008 ). Our recent study has also revealed that KRT4 expression is decreased in OSCC cells and KRT4 suppresses autophagy related 4B cysteine peptidase (ATG4B)-mediated autophagy to inhibit OSCC development ( Li et al, 2022 ). Nevertheless, the mechanism downregulating KRT4 mRNA in OSCC remains unknown.…”