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

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.