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OCC-1D regulates Wnt signaling pathway: potential role of long noncoding RNA in colorectal cancer

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Abstract

Background

Aberrant activation of the Wnt signaling pathway is observed in most colorectal cancers (CRC). OCC-1D is a splice variant of OCC-1 gene which is considered as a long noncoding RNA (lncRNA) due to lacking the translational initiation codon of the gene. Here, we sought supporting evidence for the effects of OCC-1D on the Wnt pathway and cell cycle progression in CRC.

Methods and results

TOP/FOPflash assay and qRT-PCR indicated that expression alterations of OCC-1D could change Wnt signaling activity in colon cancer cells. Consistently, immunocytochemistry results showed the effect of OCC-1D overexpression on nuclear localization of β-catenin proteins in SW480 cells. Flow cytometry, wound healing and MTT assay confirmed the cell cycle stimulatory effects of OCC-1D in CRC-originated cell lines (SW480 and HCT116). qRT-PCR revealed a positive correlation between the expression level of OCC-1D and its neighboring gene, APPL2. Two distinct tests, downregulation of APPL2 mRNA by using shRNA and Wnt signaling inhibition by using small molecule, along with OCC-1D overexpression confirmed that OCC-1D lncRNA exerts its effect on Wnt signaling pathway through expression modulation of APPL2 gene.

Conclusions

Collectively, we suggested the putative regulatory effects of OCC-1D lncRNA on cell cycle progression and Wnt signaling activation through enhancing the APPL2 gene transcription.

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Abbreviations

CRC:

Colorectal cancer

OCC-1 :

Overexpressed in Colorectal Carcinoma-1

lncRNA:

Long non-coding RNA

ICC:

Immunocytochemistry assay

APPL2 :

Adaptor Protein, Phosphotyrosine Interacting With PH Domain And Leucine Zipper 2

HDAC :

Histone deacetylase complex

GSK -3 β :

Glycogen synthase kinase3β

TCF :

Transcription Factor

shRNA:

Small hairpin RNA

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Acknowledgements

Authors thank Dr. Sadat Dokanehiifard, Zahra Shabaninejad, and Dr. Fahimeh sadat Hosseini aghdaee for their kind advices and help during performing the experiments.

Funding

This work was supported by Tarbiat Modares University (TMU) financial support.

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Authors and Affiliations

  1. Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, P.O. Box 14115-154, Tehran, Iran

    Fatemeh Yousefi, Hadi Najafi, Mehrdad Behmanesh & Bahram M. Soltani

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  1. Fatemeh Yousefi
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  2. Hadi Najafi
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  3. Mehrdad Behmanesh
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  4. Bahram M. Soltani
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Contributions

FY made the conception and design. BS participated in the development of methodology. FY performed the experiments. FY analyzed the data. FY and HN wrote the manuscript. BS reviewed and/or revised the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Bahram M. Soltani.

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Yousefi, F., Najafi, H., Behmanesh, M. et al. OCC-1D regulates Wnt signaling pathway: potential role of long noncoding RNA in colorectal cancer. Mol Biol Rep 49, 3377–3387 (2022). https://doi.org/10.1007/s11033-021-07110-5

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  • DOI: https://doi.org/10.1007/s11033-021-07110-5

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