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EVADR ceRNA transcript variants upregulate WNT and PI3K signaling pathways in SW480 and HCT116 cells by sponging miR-7 and miR-29b

  • Mohsen Yari , Bahram M. Soltani EMAIL logo , Zahra Ghaemi and Mir Davood Omrani EMAIL logo
Published/Copyright: November 25, 2022
Biological Chemistry
From the journal Biological Chemistry Volume 404 Issue 1

Abstract

Long noncoding RNAs are cancer regulators and EVADR-lncRNA is highly upregulated in colorectal cancer (CRC). Accordingly, we aimed to functionally characterize the EVADR in CRC-originated cells. Firstly, during the amplification of EVADR full-length cDNA (named EVADR-v1), a novel/shorter variant (EVADR-v2) was discovered. Then, RT-qPCR analysis confirmed that EVADR is upregulated in tumors, consistent with RNA-seq analysis. Interestingly, bioinformatics analysis and dual-luciferase assay verified that EVADR sponges miR-7 and miR-29b. When both EVADR-v1/-v2 variants were overexpressed in SW480/HCT116 cells, miR-7 and miR-29b target genes (involved in the WNT/PI3K signaling) were upregulated. Furthermore, EVADR-v1/-v2 overexpression resulted in elevated PI3K activity (verified by western blotting and RT-qPCR) and upregulation of WNT signaling (confirmed by western blotting, TopFlash assay, and RT-qPCR). Consistently, overexpression of EVADR-v1/-v2 variants was followed by increased cell cycle progression, viability and migration as well as reduced early/late apoptotic rate, and Bax/Bcl2 ratio of the CRC cells, detected by the cell cycle analysis, MTT, wound-healing, Annexin-V/PI, and RT-qPCR methods, respectively. Overall, we introduced two oncogenic transcript variants for EVADR that by sponging miR-7/miR-29b, upregulate WNT and PI3K signaling. Given the crucial role of these pathways in CRC, EVADR may present potential therapy use.

Keywords: colorectal cancer; EVADR; LncRNA; miRNAs; WNT/PI3K signaling
Corresponding authors: Bahram M. Soltani, Genetics Department, Faculty of Biological Sciences, Tarbiat Modares University, P. O. Box 14115-154, Tehran, Iran, E-mail: ; and Mir Davood Omrani, Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran, E-mail:

Funding source: Tarbiat Modares University

Award Identifier / Grant number: 964112

Acknowledgments

We express our appreciation to 4402 Lab members for their support.

  1. Author contributions: Conceptualization; M.Y., B.S and MD.O.; Data creation and analysis; M.Y., B.S and Z.G; Funding acquisition; M.Y., B.S and MD.O.; Supervision; B.S and MD.O.; All authors reviewed the results and approved the final version of the manuscript.

  2. Research funding: This study was funded by Tarbiat Modares University.

  3. Conflict of interest statement: The Authors declare that there are no competing interests associated with the manuscript.

  4. Data availability: The authors declare that the main data supporting the findings of this study are available within the article and its supplementary materials.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/hsz-2022-0246).

Received: 2022-08-04
Accepted: 2022-10-10
Published Online: 2022-11-25
Published in Print: 2023-01-27

© 2022 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Review
  3. A biochemical view on the septins, a less known component of the cytoskeleton
  4. Research Articles/Short Communications
  5. Protein Structure and Function
  6. Mathematical expressions describing enzyme velocity and inhibition at high enzyme concentration
  7. Cell Biology and Signaling
  8. MicroRNA-6838-5p suppresses the self-renewal and metastasis of human liver cancer stem cells through downregulating CBX4 expression and inactivating ERK signaling
  9. M2 macrophages-derived exosomal miR-3917 promotes the progression of lung cancer via targeting GRK6
  10. Extracellular stimulation of lung fibroblasts with arachidonic acid increases interleukin 11 expression through p38 and ERK signaling
  11. EVADR ceRNA transcript variants upregulate WNT and PI3K signaling pathways in SW480 and HCT116 cells by sponging miR-7 and miR-29b
https://doi.org/10.1515/hsz-2022-0246
Keywords for this article
colorectal cancer; EVADR; LncRNA; miRNAs; WNT/PI3K signaling

Articles in the same Issue

  1. Frontmatter
  2. Review
  3. A biochemical view on the septins, a less known component of the cytoskeleton
  4. Research Articles/Short Communications
  5. Protein Structure and Function
  6. Mathematical expressions describing enzyme velocity and inhibition at high enzyme concentration
  7. Cell Biology and Signaling
  8. MicroRNA-6838-5p suppresses the self-renewal and metastasis of human liver cancer stem cells through downregulating CBX4 expression and inactivating ERK signaling
  9. M2 macrophages-derived exosomal miR-3917 promotes the progression of lung cancer via targeting GRK6
  10. Extracellular stimulation of lung fibroblasts with arachidonic acid increases interleukin 11 expression through p38 and ERK signaling
  11. EVADR ceRNA transcript variants upregulate WNT and PI3K signaling pathways in SW480 and HCT116 cells by sponging miR-7 and miR-29b
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