<p>Intersectin 1 (ITSN1) identified by comprehensive bioinformatic analysis and experimental validation as a key candidate biological target in breast cancer</p>

Abstract

Background: As one of the most common cancers, breast carcinoma is the most common disease in women. Intersectin 1 (ITSN1) contributes to the actin cytoskeleton reconstruction in breast cancer. Purpose: The objective of this study to explore the functions of ITSN1 in breast carcinoma. Methods: We downloaded microarray datasets GSE8087, GSE50697, and GSE98238 from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were used to construct a protein-protein interaction (PPI) network using STRING database, and the modules from PPI network were verified by Cytoscape software. Gene ontology terms and Kyoto Encyclopedia of Gene and Genome pathway were used to analyze the biological functions using the DAVID database. ONCOMINE, GEPIA, UALCAN, and Human Protein Atlas databases were used to investigate the characteristics of ITSN1 for the prognosis of breast carcinoma. Cell counting kit-8, flow cytometry, and colony formation assays were used to detect cell viability, cell apoptosis, and cell proliferation. RT-PCR and Western blot assays were used to detect ITSN1, Ki67, and cleaved caspase-3 expressions. Results: Low expressions of ITSN1 were significantly associated with clinical cancer stages. RT-PCR and Western blot analysis showed low expression of ITSN1 in breast cancer tissues and cell lines. ITSN1 inhibition could promote cell proliferation and inhibit cell apoptosis, while ITSN1 overexpression could inhibit cell proliferation and increase cell apoptosis by regulating the levels of expression of Ki67 and cleaved-caspase-3. Conclusion: The results indicated that ITSN1 could be a prognostic biomarker for survivals of breast cancer patients.

Targeting Rac and Cdc42 GEFs in Metastatic Cancer

“…Structurally, N-terminal Eps15 homology (EH1 and EH2) domains, a coiled coil region, and five SH3 domains are present in the short isoform (ITSN-S), while the long isoform of ITSN (ITSN-L) has an additional C-terminal DH/PH domain, which confers GEF activity (Hunter et al, 2013). Even though low expression of ITSN1 was recently correlated with higher grade in breast and lung cancer (Xie et al, 2019;Zhang and Zhang, 2019), A role for ITSN in neuroblastoma has been shown by a study where knockdown of ITSN decreased orthotopic neuroblastoma growth in mice (Harris et al, 2017).…”

Genomic Analysis of Localized High-Risk Prostate Cancer Circulating Tumor Cells at the Single-Cell Level

“…ITSN1 inhibition is associated with cell proliferation and cell apoptosis inhibition. The ITSN1 gene is being considered a key biological target candidate for breast cancer [ 58 ]. The importance of ITSN1 deletion in prostate cancer still awaits future studies.…”

Identification of ribosomal protein family in triple-negative breast cancer by bioinformatics analysis

“…TNBC typically behaves more aggressively, worse overall survival and requires more complicated treatment approaches compared with non-TNBC [4]. Correct early diagnosis assessment of BC is very difficult, even though many cancer-related genes and cellular pathways related to BC are appeared [5]. The common treatments of BC are surgery, chemotherapy, radiotherapy and endocrine therapy such as endocrine therapy for hormone receptor positive patients and trastuzumab for HER2 positive patients, but there are no valid Downloaded from http://portlandpress.com/bioscirep/article-pdf/doi/10.1042/BSR20200869/899558/bsr-2020-0869.pdf by guest on 21 December 2020 treatment tactics available to treat TNBC [6].…”