Autophagy-Related Gene WD Repeat Domain 45B Promotes Tumor Proliferation and Migration of Hepatocellular Carcinoma through the Akt/mTOR Signaling Pathway

Abstract

Hepatocellular carcinoma (HCC) is a highly aggressive malignant tumor. It has been found that autophagy plays a role both as a tumor promoter and inhibitor in HCC carcinogenesis. However, the mechanism behind is still unveiled. This study aims to explore the functions and mechanism of the key autophagy-related proteins, to shed light on novel clinical diagnoses and treatment targets of HCC. Bioinformation analyses were performed by using data from public databases including TCGA, ICGC, and UCSC Xena. The upregulated autophagy-related gene WDR45B was identified and validated in human liver cell line LO2, human HCC cell line HepG2 and Huh-7. Immunohistochemical assay (IHC) was also performed on formalin-fixed paraffin-embedded (FFPE) tissues of 56 HCC patients from our pathology archives. By using qRT-PCR and Western blots we found that high expression of WDR45B influenced the Akt/mTOR signaling pathway. Autophagy marker LC3- II/LC3-I was downregulated, and p62/SQSTM1 was upregulated after knockdown of WDR45B. The effects of WDR45B knockdown on autophagy and Akt/mTOR signaling pathways can be reversed by the autophagy inducer rapamycin. Moreover, proliferation and migration of HCC can be inhibited after the knockdown of WDR45B through the CCK8 assay, wound-healing assay and Transwell cell migration and invasion assay. Therefore, WDR45B may become a novel biomarker for HCC prognosis assessment and potential target for molecular therapy.

ZnO nanomaterials target mitochondrial apoptosis and mitochondrial autophagy pathways in cancer cells

“…Autophagy induction can limit tumor development, but autophagy inhibition can limit the growth of established tumors and improve response to cancer treatment. 15 The replication of metabolic programming in tumors is considered a defining characteristic of cancer, as it is involved in tumor growth and cancer progression. Another notable adaptation of cancer cell metabolism is the utilization of autophagy, including specific forms like mitochondrial autophagy, to salvage intracellular components during metabolic stress or anticancer treatment.…”

“…It can maintain intracellular homeostasis and is also a survival mechanism. Autophagy induction can limit tumor development, but autophagy inhibition can limit the growth of established tumors and improve response to cancer treatment 15 …”