bims-hypusi 2023-09-03 papers

Issue of 2023‒09‒03
two papers selected by
Sebastian J. Hofer, University of Graz

Cell Death Dis. 2023 Aug 31. 14(8): 579

Targeted inhibition of eIF5Ahpu suppresses tumor growth and polarization of M2-like tumor-associated macrophages in oral cancer.

Jincheng Zeng, Ziyu Ye, Shihong Shi, Yanfang Liang, Qingyu Meng, Qunzhou Zhang, Anh D Le.

Eukaryotic initiation factor 5A2 (eIF5A2) is overexpressed in many types of cancer, and spermidine-mediated eIF5A hypusination (eIF5Ahpu) appears to be essential to most of eIF5A's biological functions, including its important role in regulating cancer cell proliferation, epithelial-mesenchymal transition (EMT), and cancer stem cell (CSC) properties as well as immune cell functions. Here we investigated the role of eIF5Ahpu in the growth of oral squamous cell carcinoma cells (OSCCs) and OSCC-induced polarization of M2-like tumor-associated macrophages (TAMs). TCGA dataset analysis revealed an overall upregulation in the mRNA expression of eIF5A2 and several key enzymes involved in polyamine (PA) metabolism in HNSCC, which was confirmed by Western blot and IHC studies. Blocking eIF5Ahpu by GC-7 but not the upstream key enzyme activities of PA metabolism, remarkably inhibited cell proliferation and the expression of EMT- and CSC-related genes in OSCC cells. In addition, blocking eIF5Ahpu robustly inhibited OSCC-induced M2-like TAM polarization in vitro. More Importantly, blocking eIF5Ahpu dramatically retarded tumor growth and infiltration/polarization of M2-like TAM in a syngeneic orthotopic murine tongue SCC model. Thus, eIF5Ahpu plays dual functions in regulating tumor cell growth and polarization of M2-TAMs in OSCC.

DOI: https://doi.org/10.1038/s41419-023-06109-z

Biochem Genet. 2023 Sep 01.

MiR-5189-3p Suppresses cell Proliferation, Invasion and Migration Through Targeting EIF5A2 in Laryngeal Squamous Cell Carcinoma.

Dan Lou, Qiaojing Jia, Haizhong Zhang, Jingmiao Wang, Lisha Liu, Zhichang Liu, Xiaofang Jia, Jianxing Wang, Chunguang Shan.

A growing body of evidence suggests that miR-5189-3p plays a critical role in multiple diseases. This study aimed to investigate the function of miR-5189-3p in laryngeal squamous cell carcinoma (LSCC) and explore its underlying mechanisms. qRT-PCR was designed to determine the expression levels of miR-5189-3p and eukaryotic translation initiation factor 5A2 (EIF5A2), while CCK-8 assay was performed to measure the effects of miR-5189-3p on cell proliferation. Transwell assay was performed to evaluate cell invasion as well as migration, and wound healing assay was applied to demonstrate cell migratory ability. Target gene prediction and luciferase reporter assay were developed to screen the possible target gene of miR-5189-3p, and Western blot was designed to measure EIF5A2 protein expression. MiR-5189-3p was down-regulated in LSCC tissues and cell lines. Up-regulation of miR-5189-3p notably inhibited cell proliferation, invasion, and migration in HEP2 and FADU cells. EIF5A2 was the potential downstream gene of miR-5189-3p, and overexpression of miR-5189-3p apparently reduced EIF5A2 expression. Moreover, reintroduction of EIF5A2 rescued the tumor suppressive effects of miR-5189-3p. MiR-5189-3p functions as a tumor inhibitor in LSCC progression via directly regulating EIF5A2 and may be a potential therapeutic target for LSCC.

Keywords: EIF5A2; Laryngeal carcinoma; Target; miR-5189-3p

DOI: https://doi.org/10.1007/s10528-023-10489-4