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Early-stage colon cancer with high MALAT1 expression is associated with the 5-Fluorouracil resistance and future metastasis

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Abstract

Background

This study aimed to investigate the role of long noncoding RNA (LncRNA) expression profiles to predict relapse and 5-FU response in patients with stage I/II colon cancer (CC).

Methods and Results

The expression level of 15 LncRNA was analyzed in stage I/II colon tumors of 126 CC patients. To confirm the findings in-vitro, 5FU-resistant HT29 cells were generated by subjecting HT-29 cells to the increasing concentrations of 5FU for 6 months. The 5FU resistance was observed in WST-1 and Annexin V analyses. The colony formation and wound healing assays were assessed to determine the metastatic properties of the cells. Expression levels of LncRNAs and mRNA of EMT-related genes were determined by RT-PCR. The role of LncRNA on metastasis and 5FU sensitivity were confirmed in pcDNA3.0-PTENP1 and si-MALAT1 expressed 5FU-resistant HT29 cell lineages.

Results

High MALAT1 (p = 0.0002) and low PTENP1 (p = 0.0044) expressions were significantly associated with 5-FU resistance and tumor relapse in stage I/II CC. The invasiveness and colony-forming characteristics of 5-FU-resistant cell lineages were higher as compared to the parent HT-29. Moreover, the expression of MALAT1 (p = 0.0009) was increased while the expression of PTENP1 (p = 0.0158) decreased in 5FU-resistant-HT-29 cells. Si-MALAT1 treatment increased cell sensitivity to 5FU, whereas it decreased invasive behaviors of 5 FU-resistant-HT-29 cells.

Conclusion

MALAT1 may be a biomarker in predicting recurrence in early-stage CC. Our findings suggest that a cell-based therapy to target MALAT1 could be established for these patients to prevent metastasis and 5-FU resistance.

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Funding

This study was funded by the Scientific Research Projects Foundation of the Bursa Uludag University, Bursa, Turkey [Grant number: KUAP(T)-2014/35, KUAP(T)-2015/2 and DDP(T)-2018/3] and the Scientific and Technical Research Council of Turkey (TUBITAK) under Grant No.318S256.

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Authors and Affiliations

  1. Vocation School of Inegol, Uludag University, Bursa, Turkey

    Secil Ak Aksoy

  2. Department of Medical Biology, Medical Faculty, Uludag University, Bursa, Turkey

    Berrin Tunca, Melis Erçelik & Gulsah Cecener

  3. Department of Fundamental Sciences, Faculty of Dentistry, Bursa Uludag University, Bursa, Turkey

    Gulcin Tezcan

  4. Department of General Surgery, Medicana, Bursa, Turkey of General Surgery, Medicana, Bursa, Turkey

    Ersin Ozturk

  5. Department of Pathology, Medical Faculty, Uludag University, Bursa, Turkey

    Nesrin Ugras & Omer Yerci

  6. Department of General Surgery, Medical Faculty, Uludag University, Bursa, Turkey

    Tuncay Yilmazlar

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  1. Secil Ak Aksoy
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  2. Berrin Tunca
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Correspondence to Berrin Tunca.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards (2014-12/16).

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Ak Aksoy, S., Tunca, B., Erçelik, M. et al. Early-stage colon cancer with high MALAT1 expression is associated with the 5-Fluorouracil resistance and future metastasis. Mol Biol Rep 49, 11243–11253 (2022). https://doi.org/10.1007/s11033-022-07680-y

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  • DOI: https://doi.org/10.1007/s11033-022-07680-y

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