RESUMEN
Study finds that eukaryotic translation initiation factor 3 subunit D (EIF3D) may play an important role in aberrant alternative splicing (AS) events in tumors. AS possesses a pivotal role in both tumour progression and the constitution of the tumour microenvironment (TME). Regrettably, our current understanding of AS remains circumscribed especially in the context of immunogene-related alternative splicing (IGAS) profiles within Head and Neck Squamous Cell Carcinoma (HNSC). In this study, we comprehensively analyzed the function and mechanism of action of EIF3D by bioinformatics analysis combined with in vitro cellular experiments, and found that high expression of EIF3D in HNSC was associated with poor prognosis of overall survival (OS) and progression-free survival (PFS). The EIF3D low expression group had a higher degree of immune infiltration and better efficacy against PD1 and CTLA4 immunotherapy compared to the EIF3D high expression group. TCGA SpliceSeq analysis illustrated that EIF3D influenced differentially spliced alternative splicing (DSAS) events involving 105 differentially expressed immunogenes (DEIGs). We observed an induction of apoptosis and a suppression of cell proliferation, migration, and invasion in EIF3D knock-down FaDu cells. RNA-seq analysis unveiled that 531 genes exhibited differential expression following EIF3D knockdown in FaDu cells. These include 52 DEIGs. Furthermore, EIF3D knockdown influenced the patterns of 1923 alternative splicing events (ASEs), encompassing 129 IGASs. This study identified an RNA splicing regulator and revealed its regulatory role in IGAS and the TME of HNSC, suggesting that EIF3D may be a potential target for predicting HNSC prognosis and immunotherapeutic response.
Asunto(s)
Empalme Alternativo , Factor 3 de Iniciación Eucariótica , Neoplasias de Cabeza y Cuello , Carcinoma de Células Escamosas de Cabeza y Cuello , Microambiente Tumoral , Humanos , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Factor 3 de Iniciación Eucariótica/genética , Factor 3 de Iniciación Eucariótica/metabolismo , Empalme Alternativo/genética , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/inmunología , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Proliferación Celular/genética , Pronóstico , Apoptosis/genética , Masculino , Movimiento Celular/genética , FemeninoRESUMEN
INTRODUCTION: Papillary thyroid microcarcinoma (PTMC) is a specific subgroup of papillary thyroid carcinoma and defined with the dimension ≤1 cm by the WHO. Although it shows a relatively high 10-year livability, the metastasis of PTMC into other tissues and organs seriously affects the daily life of patients with relatively high mortality. Therefore, the genetic basis for the metastasis of PTMC needs to be explored for effective therapeutic targets. Here, we conducted a series of comparative analysis of the transcriptional expression profile between PTMC patients with and without lymph node metastasis. METHODS: Gene expression profile and gene function were analyzed using RNA extracted from pathological tissues of 12 patients with PTMC, and the core biomarkers closely related to its metastasis were identified. RESULTS: Our results showed that 7,507 genes and 42 RNAs showed remarkably different expression patterns. More sophisticated analysis showed that the high expression of 2 lncRNAs (T077499 and T004533) resulted in the metastasis of PTMC, which suggests that the expression pattern of the 2 lncRNAs may act as a potential biomarker for pathogenesis and prognosis of PTMC metastasis. CONCLUSION: Our findings preliminarily reveal the molecular mechanisms for PTMC metastasis, which will provide vital reference for subsequent studies about the genetic basis and molecular targeted therapy for PTMC metastasis.
