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The siRNA-mediated knockdown of SNHG4 efficiently induced pro-apoptotic signaling and suppressed metastasis in SW1116 colorectal cancer cell line

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Abstract

Background

Long non-coding RNAs are broadly dysregulated in disease conditions, especially cancer, and are associated with tumor initiation, invasion, and overall survival. This study aimed to elucidate the expression level of Small Nucleolar RNA Host Gene 4 (SNHG4) lncRNA in colorectal cancer (CRC) and its effect on cell cycle progression, invasion, and death.

Methods and results

We evaluated the expression level of SNHG4 in clinical samples, including CRC tissues, adenomatous colorectal polyps (ACP), and their marginals. SNHG4-silenced SW1116 cells were used to evaluate the cell viability, cycle arrest, invasion, and apoptosis using MTT assay, scratching, flow cytometry, and immunoblotting. We also predicted molecular networks related to the SNHG4 involvement in CRC development. Results showed that SNHG4 expresses in cancerous tissues significantly higher than in polyps and marginals. This overexpression discriminated CRC from marginals and ACP with a suitable prognostic potential. Silencing of SNHG4 arrested the cell cycle at S and G2 phases and promoted early apoptosis in SW1116. It affected the active form of MMP2 and prevented cell invasion. Sponging of miRNAs which promotes the choline metabolism is the probable mechanism of SNHG4 involvement in CRC.

Conclusions

In conclusion, SNHG4 promotes CRC by dysregulating apoptosis and cell migration, and shows significant prognostic potential for CRC.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We appreciate the kind cooperation of Dr. Ghalamfarsa and his coworkers in Yasuj University of Medical Sciences, Yasuj-Iran, mainly Mis. Khosravani in preparation of SW1116 colorectal cell line.

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran

    Mina Khajehdehi & Mohammad Khalaj-Kondori

  2. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Mina Khajehdehi & Behzad Baradaran

Authors
  1. Mina Khajehdehi
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  2. Mohammad Khalaj-Kondori
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  3. Behzad Baradaran
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Contributions

Mina Khajehdehi: Writing- Original draft preparation, Investigation, Software, Methodology. Mohammad Khalaj-Kondori: Supervision, Conceptualization, Methodology, Writing- Reviewing and Editing. Behzad Baradaran: Conceptualization, Methodology.

Corresponding author

Correspondence to Mohammad Khalaj-Kondori.

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The authors have no relevant financial or non-financial interests to disclose.

Ethics approval

This study was performed in line with the principles of the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Approval was granted by the Ethics Committee of the University of Tabriz (IR.TABRIZU.REC.1398.027).

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Informed consent was obtained from all individual participants included in the study.

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The authors affirm that human research participants provided informed consent for the publication of clinicopathological characteristics in Table 1.

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Khajehdehi, M., Khalaj-Kondori, M. & Baradaran, B. The siRNA-mediated knockdown of SNHG4 efficiently induced pro-apoptotic signaling and suppressed metastasis in SW1116 colorectal cancer cell line. Mol Biol Rep 50, 8995–9006 (2023). https://doi.org/10.1007/s11033-023-08742-5

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