Identification of the inhibitor of growth protein 4 (ING4) as a potential target in prostate cancer therapy

• Published in: Molecular and cellular biochemistry Vol. 464; no. 1-2; pp. 153 - 167
• Main Authors: Shatnawi, Aymen, Malkaram, Sridhar A., Fandy, Tamer, Tsouko, Efrosini
• Format: Journal Article
• Language: English
• Published: New York Springer US 2020; Springer; Springer Nature B.V
• Subjects: Analysis; Antimitotic agents; Antineoplastic agents; Biochemistry; Biomedical and Life Sciences; Cancer; Cancer therapies; Cardiology; Care and treatment; Cell Cycle Proteins - biosynthesis; Cell Cycle Proteins - genetics; Cell Line, Tumor; Cellular communication; Chromatin; Depletion; Development and progression; Ethylenediaminetetraacetic acid; Gene expression; Gene Expression Regulation, Neoplastic; Gene regulation; Gene sequencing; Genes; Genetic transcription; Growth; Health aspects; Homeodomain Proteins - biosynthesis; Homeodomain Proteins - genetics; Humans; Inhibitors; Life Sciences; Male; Medical Biochemistry; Next-generation sequencing; Oncology; Pathogenesis; Pheochromocytoma cells; Prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Prostatic Neoplasms - therapy; Proteins; Reverse Transcriptase Polymerase Chain Reaction; Ribonucleic acid; RNA; RNA sequencing; Therapy; Transcription; Tumor Suppressor Proteins - biosynthesis; Tumor Suppressor Proteins - genetics; ING4; Gene expression; RNA-Seq; Prostate cancer; Ingenuity pathways analysis
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-019-03657-x

INhibitor of Growth protein 4 (ING4) is a potential chromatin modifier that has been implicated in several cancer-related processes. However, the role of ING4 in prostate cancer (PC) is largely unknown. This study aimed to assess ING4’s role in global transcriptional regulation in PC cells to identify potential cellular processes associated with ING4 loss. RNA-Seq using next-generation sequencing (NGS) was used to identify altered genes in LNCaP PC cells following ING4 depletion. Ingenuity pathways analysis (IPA
®
) was applied to the data to highlight candidates, ING4-regulated pathways, networks and cellular processes. Selected genes were validated using RT-qPCR. RNA-Seq of LNCaP cells revealed a total of 159 differentially expressed genes (fold change ≥ 1.5 or ≤ − 1.5, FDR ≤ 0.05) following ING4 knockdown. RT-qPCR used to validate the expression level of selected genes was in agreement with RNA-Seq results. Key genes, unique pathways, and biological networks were identified using IPA
®
analysis. This is the first report of global gene regulation in PC cells by ING4. The resultant differential expression profile revealed the potential role of ING4 in PC pathogenesis possibly through modulation of key genes, pathways and biological networks that are central drivers of the disease. Collectively, these findings shed light on a novel transcriptional regulator of PC that ultimately may influence the disease progression and as a potential target in the disease therapy.