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

  • Authors:
    • Ashish Tyagi
    • Venkatesh Kolluru
    • Balaji Chandrasekaran
    • Uttara Saran
    • Arun K. Sharma
    • Murali K. Ankem
    • Chendil Damodaran
  • View Affiliations / Copyright

    Affiliations: Department of Urology, University of Louisville, Louisville, KY 40202, USA, Department of Pharmacology, Penn State Cancer Institute, Penn State College of Medicine, Hershey, PA 17033, USA
    Copyright: © Tyagi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 850-860
    |
    Published online on: May 7, 2020
       https://doi.org/10.3892/ol.2020.11593
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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.
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Copy and paste a formatted citation
Spandidos Publications style
Tyagi A, Kolluru V, Chandrasekaran B, Saran U, Sharma AK, Ankem MK and Damodaran C: ASR488, a novel small molecule, activates an mRNA binding protein, CPEB1, and inhibits the growth of bladder cancer. Oncol Lett 20: 850-860, 2020.
APA
Tyagi, A., Kolluru, V., Chandrasekaran, B., Saran, U., Sharma, A.K., Ankem, M.K., & Damodaran, C. (2020). ASR488, a novel small molecule, activates an mRNA binding protein, CPEB1, and inhibits the growth of bladder cancer. Oncology Letters, 20, 850-860. https://doi.org/10.3892/ol.2020.11593
MLA
Tyagi, A., Kolluru, V., Chandrasekaran, B., Saran, U., Sharma, A. K., Ankem, M. K., Damodaran, C."ASR488, a novel small molecule, activates an mRNA binding protein, CPEB1, and inhibits the growth of bladder cancer". Oncology Letters 20.1 (2020): 850-860.
Chicago
Tyagi, A., Kolluru, V., Chandrasekaran, B., Saran, U., Sharma, A. K., Ankem, M. K., Damodaran, C."ASR488, a novel small molecule, activates an mRNA binding protein, CPEB1, and inhibits the growth of bladder cancer". Oncology Letters 20, no. 1 (2020): 850-860. https://doi.org/10.3892/ol.2020.11593
Copy and paste a formatted citation
x
Spandidos Publications style
Tyagi A, Kolluru V, Chandrasekaran B, Saran U, Sharma AK, Ankem MK and Damodaran C: ASR488, a novel small molecule, activates an mRNA binding protein, CPEB1, and inhibits the growth of bladder cancer. Oncol Lett 20: 850-860, 2020.
APA
Tyagi, A., Kolluru, V., Chandrasekaran, B., Saran, U., Sharma, A.K., Ankem, M.K., & Damodaran, C. (2020). ASR488, a novel small molecule, activates an mRNA binding protein, CPEB1, and inhibits the growth of bladder cancer. Oncology Letters, 20, 850-860. https://doi.org/10.3892/ol.2020.11593
MLA
Tyagi, A., Kolluru, V., Chandrasekaran, B., Saran, U., Sharma, A. K., Ankem, M. K., Damodaran, C."ASR488, a novel small molecule, activates an mRNA binding protein, CPEB1, and inhibits the growth of bladder cancer". Oncology Letters 20.1 (2020): 850-860.
Chicago
Tyagi, A., Kolluru, V., Chandrasekaran, B., Saran, U., Sharma, A. K., Ankem, M. K., Damodaran, C."ASR488, a novel small molecule, activates an mRNA binding protein, CPEB1, and inhibits the growth of bladder cancer". Oncology Letters 20, no. 1 (2020): 850-860. https://doi.org/10.3892/ol.2020.11593
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