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SLED1 Promoting Cell Proliferation and Inhibiting Apoptosis in Acute Myeloid Leukemia: a Study

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Abstract

In this study, we aimed to explore long non-coding RNA (lncRNA) sustained low-efficiency dialysis (SLED1) correlated with Bcl-2 apoptosis pathway in acute myeloid leukemia (AML). This study further aimed to determine its role in the regulation of AML progression and its action as a potential biomarker for better prognosis. AML microarray profiles GSE97485 and probe annotation from the Gene Expression Omnibus (GEO) database from the National Center for Biotechnology Information (NCBI) were detected using the GEO2R tool (http://www.ncbi.nlm.nih.gov/geo/geo2r/). The expression of AML was downloaded from the TCGA database (http://cancergenome.nih.gov/). The statistical analysis of the database was processed with R software. Bioinformatic analysis found that lncRNA SLED1 is highly expressed in AML patients and is associated with poor prognosis. We found that the increased SLED1 expression levels in AML were significantly correlated with FAB classification, human race, and age. Our study has shown that upregulation of SLED1 promoted AML cell proliferation and inhibited cell apoptosis in vitro; RNA sequencing showed increased expression of BCL-2 and indicated that SLED1 might promote the development of AML by regulating BCL-2. Our results showed that SLED1 could promote the proliferation and inhibit the apoptosis of AML cells. SLED1 might promote the development of AML by regulating BCL-2, but the mechanism involved in the progression of AML is unclear. SLED1 plays an important role in AML progression, may be applied as a rapid and economical AML prognostic indicator to predict the survival of AML patients, and help guide experiments for potential clinical drag targets.

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Data Availability

The datasets supporting the conclusions of this article are available in the Gene Expression Omnibus repository (GSE97485; https://www.ncbi.nlm.nih.gov/geo/ query/acc.cgi?acc = GSE97485) and the TCGA database (http://cancergenome.nih.gov/). The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

AML:

Acute myeloid leukemia

lncRNAs:

Long non-coding RNAs

SLED1:

Sustained low-efficiency dialysis

RNA:

Ribonucleic acid

References

  1. Prada-Arismendy, J., Arroyave, J. C., & Röthlisberger, S. (2017). Molecular biomarkers in acute myeloid leukemia. Blood Reviews, 31(1), 63–76.

    Article  PubMed  CAS  Google Scholar 

  2. Yi, M., Li, A., Zhou, L., Chu, Q., Song, Y., & Wu, K. (2020). The global burden and attributable risk factor analysis of acute myeloid leukemia in 195 countries and territories from 1990 to 2017: Estimates based on the global burden of disease study 2017. Journal of Hematology & Oncology, 13(1), 1–16.

    Article  Google Scholar 

  3. Kouchkovsky, I. D., & Abdul-Hay, M. (2016). Acute myeloid leukemia: A comprehensive review and 2016 update. Blood Cancer J, 6(7), e441.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Medinger, M., Heim, D., Halter, J. P., Lengerke, C., & Passweg, J. R. (2019). Diagnostik und Therapie der Akuten Myeloischen Leukämie [Diagnosis and therapy of acute myeloid leukemia]. Therapeutische Umschau, 76(9), 481–486.

    Article  PubMed  Google Scholar 

  5. Sami, S. A., Darwish, N. H. E., Barile, A. N. M., & Mousa, S. A. (2020). Current and future molecular targets for acute myeloid leukemia therapy. Current Treatment Options in Oncology, 21(1), 1–16.

    Article  Google Scholar 

  6. Song, Y. P. (2012). Process in the treatment of senile acute leukemia. Journal of Clinical Hematology, 25(9), 547–549.

    Google Scholar 

  7. Xiang, J., Guo, S., Jiang, S., Xu, Y., Li, J., Li, L., & Xiang, J. (2016). Silencing of long non-coding RNA MALAT1 promotes apoptosis of glioma cells. Journal of Korean Medical Science, 31(5), 688–694.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Adams, B. D., Parsons, C., Walker, L., Zhang, W. C., & Slack, F. J. (2017). Targeting noncoding RNAs in disease. The Journal of Clinical Investigation, 127(3), 761–771.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Chen, T., Wang, H., Yang, P., & He, Z. Y. (2017). Prognostic role of long noncoding RNA NEAT1 in various carcinomas: A meta-analysis. Oncotargets and Therapy, 10, 993–1000.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Estey, E. (2009). AML in older patients: Are we making progress? Best Practice & Research. Clinical Haematology, 22(4), 529–536.

    Article  Google Scholar 

  11. Fathi, A. T., Wander, S. A., Blonquist, T. M., Brunner, A. M., Amrein, P. C., Supko, J., Hermance, N. M., Manning, A. L., Sadrzadeh, H., Ballen, K. K., Attar, E. C., Graubert, T. A., Hobbs, G., Joseph, C., Perry, A. M., Burke, M., Silver, R., Foster, J., Bergeron, M., … Chen, Y. (2017). Phase I study of the aurora A kinase inhibitor alisertib with induction chemotherapy in patients with acute myeloid leukemia. Haematologica, 102(4), 719–727.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Wang, X., Zhang, Z., Wang, H., Cai, J., Xu, Q., Li, M., Chen, Y., Qian, X., Lu, T., Yu, L., Zhang, Y., Xin, D., Na, Y., & Chen, W. (2006). Rapid identification of UCA1 as a very sensitive and specific unique marker for human bladder carcinoma. Clinical Cancer Research, 12(16), 4851–4858.

    Article  PubMed  CAS  Google Scholar 

  13. Sun, L., Li, X., Sun, Y., Huang, W., Fang, K., Han, C., Chen, Z., Luo, X., Chen, Y., & Wang, W. (2018). LncRNA ANRIL regulates AML development through modulating the glucose metabolism pathway of AdipoR1/AMPK/SIRT1. Molecular Cancer, 127(17), 1–6.

    CAS  Google Scholar 

  14. Zhang, T. J., Zhou, J. D., Zhang, W., Lin, J., Ma, J. C., Wen, X. M., Yuan, Q., Li, X. X., Xu, Z. J., & Qian, J. (2018). H19 overexpression promotes leukemogenesis and predicts unfavorable prognosis in acute myeloid leukemia. Clinical Epigenetics, 47(10), 1–12.

    Google Scholar 

  15. Guo, H., Wu, L., Zhao, P. U., & Feng, A. (2017). Overexpression of long non-coding RNA zinc finger antisense 1 in acute myeloid leukemia cell lines influences cell growth and apoptosis. Experimental and Therapeutic Medicine, 14(1), 647–651.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Zhang, X., & Tao, W. (2019). Long noncoding RNA LINC00152 facilitates the leukemogenesis of acute myeloid leukemia by promoting CDK9 through miR-193a. DNA and Cell Biology, 38(3), 236–242.

    Article  PubMed  CAS  Google Scholar 

  17. Ma, L., Kuai, W., Sun, X., Lu, X., & Yuan, Y. (2018). Long noncoding RNA LINC00265 predicts the prognosis of acute myeloid leukemia patients and functions as a promoter by activating PI3K-AKT pathway. European Review for Medical and Pharmacological Sciences, 22(22), 7867–7876.

    PubMed  CAS  Google Scholar 

  18. Dong, X., Fang, Z., Yu, M., Zhang, L., Xiao, R., Li, X., Pan, G., & Liu, J. (2018). Knockdown of long noncoding RNA HOXA-AS2 suppresses chemoresistance of acute myeloid leukemia via the miR-520c-3p/S100A4 axis. Cellular Physiology and Biochemistry, 51(2), 886–896.

    Article  PubMed  CAS  Google Scholar 

  19. Zhao, C., Wang, S., Zhao, Y., Du, F., Wang, W., Lv, P., & Qi, L. (2019). Long noncoding RNA NEAT1 modulates cell proliferation and apoptosis by regulating miR-23a-3p/SMC1A in acute myeloid leukemia. Journal of Cellular Physiology, 234(5), 6161–6172.

    Article  PubMed  CAS  Google Scholar 

  20. Goswami, M., Prince, G., Biancotto, A., Moir, S., Kardava, L., Santich, B. H., Cheung, F., Kotliarov, Y., Chen, J., Shi, R., Zhou, H., Golding, H., Manischewitz, J., King, L., Kunz, L. M., Noonan, K., Borrello, I. M., Smith, B. D., & Hourigan, C. S. (2017). Impaired B cell immunity in acute myeloid leukemia patients after chemotherapy. Journal of Translational Medicine, 15(155), 1–16.

    Google Scholar 

  21. Fujita, A., Sato, J. R., Rodrigues, L. D. O., Ferreira, C. E., & Sogayar, M. C. (2006). Evaluating different methods of microarray data normalization. BMC Bioinformatics., 7(469), 1–11.

    Google Scholar 

  22. Tang, Z., Li, C., Kang, B., Gao, G., Li, C., & Zhang, Z. (2017). GEPIA: A web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Research, 45(W1), W98–W102.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Chandrashekar, D. S., Bashel, B., Balasubramanya, S. A. H., Creighton, C. J., Ponce-Rodriguez, I., Chakravarthi, B. V. S. K., & Varambally, S. (2017). UALCAN: A portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia, 19(8), 649–658.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Büchner, T., Berdel, W. E., Haferlach, C., Haferlach, T., Schnittger, S., Müller-Tidow, C., Braess, J., Spiekermann, K., Kienast, J., Staib, P., Grüneisen, A., Kern, W., Reichle, A., Maschmeyer, G., Aul, C., Lengfelder, E., Sauerland, M., Heinecke, A., Wörmann, Be., & Hiddemann, W. (2009). Age-related risk profile and chemotherapy dose response in acute myeloid leukemia: A study by the German Acute Myeloid Leukemia Cooperative Group. J Clin Oncol., 27(1), 61–69.

    Article  PubMed  Google Scholar 

  25. Appelbaum, F. R., Gundacker, H., Head, D. R., Slovak, M. L., Willman, C. L., Godwin, J. E., Anderson, J. E., & Petersdorf, S. H. (2006). Age and acute myeloid leukemia. Blood, 107(9), 3481–3485.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Döhner, H., Estey, E. H., Amadori, S., Appelbaum, F. R., Büchner, T., Burnett, A. K., Dombret, H., Fenaux, P., Grimwade, D., Larson, R. A., Lo-Coco, F., Naoe, T., Niederwieser, D., Ossenkoppele, G. J., Sanz, M. A., Sierra, J., Tallman, M. S., Löwenberg, B., & Bloomfield, C. D. (2010). Diagnosis and management of acute myeloid leukemia in adults: Recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood, 115(3), 453–474.

    Article  PubMed  Google Scholar 

  27. Patel, J. P., Gönen, M., Figueroa, M. E., Fernandez, H., Sun, Z., Racevskis, J., Vlierberghe, P. V., Dolgalev, I., Thomas, S., Aminova, O., Huberman, K., Cheng, J., Viale, A., Socci, N. D., Heguy, A., Cherry, A., Vance, G., Higgins, R. R., Ketterling, R. P., … Levine, R. L. (2013). Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med, 336(12), 296–298.

    Google Scholar 

  28. Gilliland, D. G., & Geiffin, J. D. (2002). The roles of FLT3 in hematopoiesis and leukemia. Blood, 100(5), 1532–1542.

    Article  PubMed  CAS  Google Scholar 

  29. Takahashi, S. (2011). Current findings for recurring mutations in acute myeloid leukemia. Journal of Hematology & Oncology, 36(4), 1–11.

    Google Scholar 

  30. Kihara, R., Nagata, Y., Kiyoi, H., Kato, T., Yamamoto, E., Suzuki, K., Chen, F., Asou, N., Ohtake, S., Miyawaki, S., Miyazaki, Y., Sakura, T., Ozawa, Y., Usui, N., Kanamori, H., Kiguchi, T., Imai, K., Uike, N., Kimura, F., … Naoe, T. (2014). Comprehensive analysis of genetic alterations and their prognostic impacts in adult acute myeloid leukemia patients. Leukemia, 28(8), 1586–1595.

    Article  PubMed  CAS  Google Scholar 

  31. Scholl, C., Gilliland, D. G., & Fröhling, S. (2008). Deregulation of signaling pathways in acute myeloid leukemia. Seminars in Oncology, 35(4), 336–345.

    Article  PubMed  CAS  Google Scholar 

  32. Cook, A. M., Li, L., Ho, Y., Lin, A., & Li, L. (2014). Anthony Stein, Stephen Forman, Danilo Perrotti, Richard Jove, and Ravi Bhatia, Role of altered growth factor receptor-mediated JAK2 signaling in growth and maintenance of human acute myeloid leukemia stem cells. Blood, 123(18), 2826–2837.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Gupta, S. G., Baumann, H., & Wetzler, M. (2008). Epigenetic regulation of signal transducer and activator of transcription 3 in acute myeloid leukemia. Leukemia Research, 32(7), 1005–1014.

    Article  Google Scholar 

  34. Yamada, O., & Kawauchi, K. (2013). The role of the JAK-STAT pathway and related signal cascades in telomerase activation during the development of hematologic malignancies. Jakstat, 2(4), e25256.

    PubMed  PubMed Central  Google Scholar 

  35. Schuringa, J. J., Wierenga, A. T., Kruijer, W., & Vellenga, E. (2000). Constitutive Stat3, Tyr705, and Ser727 phosphorylation in acute myeloid leukemia cells caused by the autocrine secretion of interleukin-6. Blood, 95(12), 3765–3770.

    Article  PubMed  CAS  Google Scholar 

  36. Spiekermann, K., Bagrintseva, K., Schwab, R., Schmieja, K., & Hiddemann, W. (2003). Overexpression and constitutive activation of FLT3 induces STAT5 activation in primary acute myeloid leukemia blast cells. Clinical Cancer Research, 9(6), 2140–2150.

    PubMed  CAS  Google Scholar 

  37. Miyashita, T., Krajewski, S., Krajewska, M., Wang, H. G., Lin, H. K., Liebermann, D. A., Hoffman, B., & Reed, J. C. (1994). Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. Oncogene, 9(6), 1799–1805.

    PubMed  CAS  Google Scholar 

  38. Konopleva, M., & Letai, A. (2018). BCL-2 inhibition in AML: An unexpected bonus? Blood, 132(10), 1007–1012.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Hockenbery, D. M. (2010). Targeting mitochondria for cancer therapy. Environmental and Molecular Mutagenesis, 51(5), 476–489.

    Article  PubMed  CAS  Google Scholar 

  40. de Almagro, M. C., & Vucic, D. (2012). The inhibitor of apoptosis (IAP) proteins are critical regulators of signaling pathways and targets for anti-cancer therapy. Experimental Oncology, 34(3), 200–211.

    PubMed  Google Scholar 

  41. Letai, A., Bassik, M. C., Walensky, L. D., Sorcinelli, M. D., Weiler, S., & Korsmeyer, S. J. (2002). Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics. Cancer Cell, 2(3), 183–192.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

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Funding

The study was supported by grants from the award of the China Scholarship Council Visiting Scholar Grant to Jimo Jian (No. 201906225042) and The Youth Scientific Foundation of Qilu Hospital (Qingdao) of Shandong University (No. QDKY2015QN10).

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Authors

Contributions

Conceptualization, Jimo Jian; formal analysis, Jimo JianNana Wang and Hongyuan Hao; methodology, Jimo Jian, Hongyuan Hao, and Qian Liu; project administration, Chenglu Yuan and Chunyan Ji; supervision, Fei Lu; writing—original draft, Jimo Jian; writing—review and editing, Fei Lu. All of the authors have read and approved the manuscript.

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Correspondence to Fei Lu.

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This study was approved by the clinical ethics board of Qilu Hospital (Qingdao), Shandong University (KYLL-KS-2021171).

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Jian, J., Wang, N., Hao, H. et al. SLED1 Promoting Cell Proliferation and Inhibiting Apoptosis in Acute Myeloid Leukemia: a Study. Appl Biochem Biotechnol 195, 6633–6652 (2023). https://doi.org/10.1007/s12010-023-04421-0

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