Microarray pathway analysis indicated that mitogen-activated protein kinase/extracellular signal-regulated kinase and insulin growth factor 1 signaling pathways were inhibited by small interfering RNA against AT‑rich interactive domain 1A in endometrial cancer

Abstract

Abstract. Mutations in the gene encoding AT-rich interactive domain 1A (ARID1A) are frequently observed in endometrial cancer (EC) but the molecular mechanisms linking the genetic changes remain to be fully understood. The present study aimed to elucidate the influence of ARID1A mutations on signaling pathways. Missense, synonymous and nonsense heterozygous ARID1A mutations in the EC HEC-1-A cell line were verified by Sanger sequencing. Mutated ARID1A small interfering RNA was transfected into HEC-1-A cells. Biochemical microarray analysis revealed 13 upregulated pathways, 17 downregulated pathways, 14 significantly affected disease states and functions, 662 upstream and 512 downstream genes in mutated ARID1A-depleted HEC-1-A cells, among which the mitogen-activated protein kinase/extracellular signal-regulated kinase and insulin-like growth factor-1 (IGF1) signaling pathways were the 2 most downregulated pathways. Furthermore, the forkhead box protein O1 pathway was upregulated, while the IGF1 receptor, insulin receptor substrate 1 and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit b pathways were downregulated. Carcinoma tumorigenesis, tumor cell mitosis and tumor cell death were significantly upregulated disease states and functions, while cell proliferation and tumor growth were significantly downregulated. The results of the present study suggested that ARID1A may be a potential prognostic and therapeutic molecular drug target for the prevention of EC progression.

BZW2 gene knockdown induces cell growth inhibition, G1 arrest and apoptosis in muscle‐invasive bladder cancers: A microarray pathway analysis

“…On the above basis, we used IPA tools (http://www.ingenuity.com) to identify differentially expressed canonical pathways by defining the enrichment P ‐value of the pathway. Signalling pathways associated with BZW2‐knockdown cells were sequenced by their ‐Log( P ‐value) (Figure B) Notably, several pathways were found to be associated with cell cycle, including cyclins and cell cycle regulation, oestrogen‐mediated S‐phase entry, G2/M DNA damage checkpoint regulation, mitotic roles of PLK, ATM signalling . This is in agreement with the above experimental observations that BZW2‐knockdown induces G1‐phase cell cycle arrest in T24 cells.…”

“…Expression data were normalized by quantile normalization. All gene level files were imported into Ingenuity Pathway Analysis (IPA) software (Qiagen GmbH, Hilden, Germany) for further analysis according to previous report. Specifically, the distributions of the intensities of six samples and the similarities between BZW2‐knockdown (KD) and normal control (NC) groups were examined by principal component analysis (Figure ) and Pearson's correlation of the signal value (Figure ).…”

ARID1A-deficient bladder cancer is dependent on PI3K signaling and sensitive to EZH2 and PI3K inhibitors

“…Experiments are underway to determine these mechanisms. Downregulation of MAPK pathways in ARID1Adeficient endometrial carcinoma has been described (43), but whether this is universal amongst ARID1A-deficient tumors remains to be determined.…”

Network Pharmacology-Based and Molecular Docking Analysis of Resveratrol’s Pharmacological Effects on Type I Endometrial Cancer

“…MAPK1/MAPK3 belong to the Mitogen-activated protein kinases (MAPK) family, an important family of protein kinases involved in transmitting signals from the cell membrane to the nucleus. They play an important role in MAPK/ERK cascade, mediating diverse biological functions, including initiation of endometrial oncogenesis [ 45 ]. Mitogen-activated protein kinase 8 (MAPK8, also known as JNK1, c-Jun N-terminal kinases), acts to phosphorylate a number of transcription factors, including JUN, JDP2, ATF2, etc ., thereby involved in the various biological process such as cell proliferation, differentiation, migration, transformation and programmed cell death [ 46 ].…”