ASR488, a novel small molecule, activates an mRNA binding protein, CPEB1, and inhibits the growth of bladder cancer

Ashish Tyagi, Venkatesh Kolluru, Balaji Chandrasekaran, Uttara Saran, Arun K. Sharma, Murali K. Ankem, Chendil Damodaran

Research output: Contribution to journalArticle

Abstract

Due to a lack of mechanistic insights, muscle-invasive bladder cancer (MIBC) remains incurable and is one of the most lethal types of cancer in the United States. The present study investigated changes in the molecular signatures of MIBC cells (TCCSUP and HT1376) after treatment with a novel small molecule, ASR488, to gain knowledge of the mechanisms that inhibited MIBC cell growth. ASR488 treatment initiated apoptotic signaling in MIBC cells. Pathway enrichment analysis was used to analyze the changes in function of differentially expressed genes. Gene Ontology analysis, as well as Kyoto Encyclopedia of Genes and Genomes analysis, was also performed. These analyses along with reactome pathway enrichment analyses indicated that the genes upregulated in the ASR488-treated cells are involved in focal adhesion, neurotrophin signaling, p53 signaling, endoplasmic reticulum functioning in terms of protein processing, and pathways related to bladder cancer. The genes downregulated in ASR488-treated MIBC cells were mainly involved in DNA replication, mismatch repair, RNA degradation, nucleotide excision repair and TGFβ signaling (P<0.05). Furthermore, reverse transcription-quantitative PCR analysis revealed an increase in transcripts of the most upregulated genes in ASR 488-treated MIBC cells: CPEB1 (36-fold), IL11 (30-fold), SFN (20.12-fold) and CYP4F11 (15.8-fold). In conclusion, the analysis of biological functions of the most differentially expressed genes revealed possible mechanisms that may be associated with the aggressiveness of MIBC.

Original languageEnglish (US)
Pages (from-to)850-860
Number of pages11
JournalOncology Letters
Volume20
Issue number1
DOIs
StatePublished - Jul 2020

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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