Multi-omic analysis reveals HIP-55-dependent regulation of cytokines release.

Yunqi Jiang,Zhi Shi,Zihao Xing,Wenjing Wang,Baolin Zhu,Yang Sun,Zijian Li

doi:10.1042/bsr20200298

Abstract

HIP-55 (HPK1 [hematopoietic progenitor kinase 1] -interacting protein of 55 kDa) contains an actin-depolymerizing factor homology (ADF-H) domain at the N-terminus and a src homology 3 (SH3) domain at the C-terminus, which plays an important role in the T cell receptor (TCR) and B-cell receptor (BCR) signaling and immune system. In our previous studies, HIP-55 was found to be highly expressed in several types of tumors and function as a novel oncogenic signaling hub that regulates tumor progression and metastasis through defined functional domains, actin-binding and SH3 modules. However, the wider functions and mechanisms of HIP-55 are still unclear. Here, multi-omic analysis revealed that one of the main biofunctions of HIP-55 is the regulation of cytokines release. Furthermore, to investigate the role of HIP-55 in the cytokine production, a series Cytokine Antibody Arrays were performed to detect differentially expressed cytokines between control and HIP-55 knockdown cells. A total of 97 differentially expressed cytokines were identified from 300 cytokines in A549 cell. Bioinformatics analysis showed these differentially cytokines were mainly enriched in cancer signal pathways and IL-6 is the most critical hub in the integrated network. Analysis of RNAseq data from lung cancer patients showed that there is a strong negative correlation between HIP-55 and interleukin-6 (IL-6) in samples from lung adenocarcinoma patients. Our data indicated that HIP-55 may participate in cancer progression and metastasis via regulating cytokines release.

Highlights

Cancer is one of the leading causes of death in worldwide for its extreme complex pathogenesis and rapid progression, and its incidence is still increasing in recent years
Bioinformatics analysis of the differentially expressed genes associated with down-regulation of hematopoietic progenitor kinase 1 (HPK1)-hematopoietic progenitor kinase 1 (HIP-55)
In order to study the biological function of HIP-55 and to identify additional protein targets for HIP-55 in A549 cells, mRNA microarray was applied to in both HIP-55 knockdown cells and the control cells (Figure 1A)

Summary

Introduction

Cancer is one of the leading causes of death in worldwide for its extreme complex pathogenesis and rapid progression, and its incidence is still increasing in recent years. Though progress in early diagnostic biomarkers and precise treatments have been achieved, the average 5-year survival rates for malignant is still low [1]. Our previous studies have demonstrated that HIP-55 were over-expressed in several types of tumor tissues, such as thyroid cancer and lung cancer [4,5]. HIP-55 showed significant promotive effects in the proliferative and invasive activity of lung cancer cells and the apoptosis-inhibiting effects on A549 cells [4,5]. Our accumulative evidence suggested that HIP-55 may be important for tumorigenesis and progression. The detailed mechanisms of HIP-55 participated in cancer were still unclear

Methods

Results

Conclusion