YY1 regulated transcription‐based stratification of gastric tumors and identification of potential therapeutic candidates | Zendy

Bhaskar Rao Divya | Zendy; Panneerpandian Ponmathi | Zendy; Balakrishnan Karthik | Zendy; Ganesan Kumaresan | Zendy

Open Access

YY1 regulated transcription‐based stratification of gastric tumors and identification of potential therapeutic candidates

Author(s) -

Bhaskar Rao Divya,

Panneerpandian Ponmathi,

Balakrishnan Karthik,

Ganesan Kumaresan

Publication year - 2021

Publication title -

journal of cell communication and signaling

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.329

H-Index - 44

eISSN - 1873-961X

pISSN - 1873-9601

DOI - 10.1007/s12079-021-00608-4

Subject(s) - wnt signaling pathway , gene silencing , cancer research , transcription factor , yy1 , biology , carcinogenesis , cancer , mapk/erk pathway , gene , promoter , gene expression , signal transduction , genetics

Gastric cancer is one of the leading causes of cancer‐related death worldwide. The transcription factor YY1 regulates diverse biological processes, including cell proliferation, development, DNA damage responses, and carcinogenesis. This study was designed to explore the role of YY1 regulated transcription in gastric cancer. YY1 silencing in gastric cancer cells has resulted in the inhibition of Wnt/ β ‐catenin, JNK/MAPK, ERK/MAPK, ER, and HIF‐1α signaling pathways. Genome‐wide mRNA profiling upon silencing the expression YY1 gene in gastric cancer cells and comparison with the previously identified YY1 regulated genes from other lineages revealed a moderate overlap among the YY1 regulated genes. Despite the differing genes, all the YY1 regulated gene sets were expressed in most of the intestinal subtype gastric tumors and a subset of diffuse subtype gastric tumors. Integrative functional genomic analysis of the YY1 gene sets revealed an association among the pathways Wnt/β‐catenin, Rapamycin, Cyclin‐D1, Myc, E2F, PDGF, and AKT. Further, the drugs capable of inhibiting YY1 mediated transcription were identified as suitable targeted therapeutic candidates for gastric tumors with activated YY1. The data emerging from the investigation would pave the way for the development of YY1‐based targeted therapeutics for gastric cancer.

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