TBC1D14 inhibits autophagy to suppress lymph node metastasis in head and neck squamous cell carcinoma by downregulating macrophage erythroblast attacher

Abstract

Aims: This study aimed to identify the correlation and molecular mechanism between TBC1 domain family member 14 (TBC1D14) and lymph node metastasis (LNM) in head and neck squamous cell carcinoma (HNSCC). Methods: Whole transcriptome sequencing of HNSCC tissues with or without LNM was performed. TBC1D14 expression was quantified in HNSCC tissues. The role of TBC1D14 in HNSCC migration, invasion, autophagy, and LNM was investigated by wound healing, Transwell, western blotting, immunofluorescence, and transmission electron microscopy assays in vitro and in a mouse model in vivo. The correlation between autophagy and LNM was detected by wound healing and Transwell assays in vitro and western blotting in vivo. Mass spectrometry was used to identify the downstream target proteins. The correlation between TBC1D14 expression and macrophage erythroblast attacher (MAEA) expression was identified by qRT-PCR and western blotting assays in vitro and immunohistochemistry in vivo. The gain-of-function strategy was applied to further reveal the role of MAEA in the TBC1D14-induced autophagy of HNSCC cells. Results: TBC1D14 was a co-differentially expressed gene in the sequencing results, The Cancer Genome Atlas Data Portal, and Gene Expression Omnibus databases. TBC1D14 had a lower RNA and protein expression in HNSCC with LNM samples and was a favorable prognostic indicator. TBC1D14 inhibited the migration and invasion of HNSCC in vivo. Mechanistically, TBC1D14-induced autophagy suppression inhibited the migration and invasion of HNSCC. TBC1D14 expression negatively correlated with MAEA expression both in vitro and in vivo. Furthermore, MAEA overexpression could reverse TBC1D14-induced autophagy suppression. Conclusion: TBC1D14 is a novel LNM inhibitor in HNSCC and a favorable prognostic marker. TBC1D14 suppresses autophagy to inhibit LNM in HNSCC by downregulating MAEA expression. The results clarify the molecular mechanism of TBC1D14 in HNSCC.

Non-coding transcriptomic profiles in the sheep mammary gland during different lactation periods

“…Specifically, the expression level of novel_circ_0010160 rapidly decreased from the PP to the EL and then slowly increased from EL to PL. Previous studies on TBC1D14 (parental gene of novel_circ_0010160) demonstrated its important role in cancer cell autophagy ( 43 , 44 ). This evidence suggests that novel_circ_0010160 may also function similarly in sheep MEC autophagy and would make a prime candidate for future research, especially in the non-lactation period.…”

Glia Maturation Factor β as a Novel Independent Prognostic Biomarker and Potential Therapeutic Target of Kidney Renal Clear Cell Carcinoma

“…Consistent with the results from the meta-analysis, INAFM1, HCFC1R1, and METTL26 were downregulated, and ATP6V0D2, TBC1D14, OXCT1, ALDH6A1, FAM160A1, and NCR3LG1 were upregulated in GMFB overexpressed Caki-2 cells ( Figures 5C, D ). The validated DEGs with GMFB co-expression may participate in multiple pathways in KIRC biology, including enhancing response in KIRC cell to NK cell (NCR3LG1) ( 46 ), negatively regulating autophagy (TBC1D14) ( 47 ), and being regulated by lactate (ATP6V0D2) ( 48 ) in TMEs.…”

Effect of regulatory cell death on the occurrence and development of head and neck squamous cell carcinoma

“…In HNSCC, TBC1D14 inhibits autophagy by downregulating the expression of MAEA. Overexpression of TBC1D14 inhibits autophagy by reducing the level of Lc3-II protein, increasing the level of p62 protein, and inhibiting the formation of autolysosomes, thus playing a role in anti-HNSCC metastasis [ 97 – 99 ]. Circ-PKD2 can increase the sensitivity of oral squamous cell carcinoma to cisplatin by inhibiting miR-646.…”