RNA-binding protein RBPMS regulates proliferation and migration of acute myeloid leukemia cells line THP-1

doi:10.16352/j.issn.1001-6325.2024.05.0619

Abstract

Abstract: Objective To investigate the impact of the RNA-binding protein with multiple splicing(RBPMS), which has multiple splicing functions, on the function of acute myeloid leukemia cells line THP-1 carrying the MLL-AF9 fusion gene. Methods The expression of RBPMS in the hematopoietic system was analyzed using the GEO database; RBPMS over-expression in THP-1 cells was achieved through lentiviral infection. The efficiency was detected by RT-qPCR and Western blot; The effect of RBPMS over-expression on the THP-1 cell transcriptome was evaluated by high-throughput sequencing. The impact of RBPMS over-expression on the proliferation and migration of leukemia cells was examined using CCK-8 assay and flow cytometry, respectively. Results RBPMS expressed in acute myeloid leukemia stem cells carrying the MLL-AF9 fusion gene was found to be inhibited. Over-expression of RBPMS significantly reduced the proliferation and migration of THP-1 cells. Conclusions RBPMS inhibits cell proliferation and migration of acute myeloid leukemia cells line carrying the MLL-AF9 fusion gene.

Key words: RBPMS, MLL-AF9, acute myeloid leukemia, acute monocytic leukemia cells line(THP-1)

CLC Number:

R733.7

ZHAO Lingyan, HE Liu, MA Yanni, YU Jia. RNA-binding protein RBPMS regulates proliferation and migration of acute myeloid leukemia cells line THP-1[J]. Basic & Clinical Medicine, 2024, 44(5): 619-625.

References

[1] DiNardo CD, Erba HP, Freeman SD, et al. Acute myeloid leukaemia[J]. The Lancet, 2023, 401: 2073-2086.doi:10.1016/S0140-6736(23)00108-3.
[2] Meyer C, Burmeister T, Gröger D, et al. The MLL recombinome of acute leukemias in 2017[J]. Leukemia, 2018,32: 273-284.doi:10.1038/leu.2017.213.
[3] Muntean AG, Hess JL. The pathogenesis of mixed-lineage leukemia[J]. Annu Rev Pathol, 2012,7: 283-301.doi:10.1146/annurev-pathol-011811-132434.
[4] Winters AC, Bernt KM. MLL-rearranged leukemias—an update on science and clinical approaches[J].Front Pediatr, 2017, 5:4.doi:10.3389/fped.2017.00004.
[5] Shimamoto A, Kitao S, Ichikawa K, et al.A unique human gene that spans over 230 kb in the human chromosome 8p11-12 and codes multiple family proteins sharing RNA-binding motifs[J].Proc Natl Acad Sci U S A, 1996, 93:10913-10917.doi:10.1073/pnas.93.20.10913.
[6] Fu J, Cheng L, Wang Y, et al.The RNA-binding protein RBPMS1 represses AP-1 signaling and regulates breast cancer cell proliferation and migration[J].Biochim Biophys Acta,2015, 1853:1-13.doi:10.1016/j.bbamcr.2014.09.022.
[7] Yan S, Lihua D, Hao Z, et al.Potentiation of Smad-mediated transcriptional activation by the RNA-binding protein RBPMS[J].Nucleic Acids Res, 2006, 34:6314-6326.doi:10.1093/nar/gkl914.
[8] Rabelo-Fernández RJ, Noriega Rivera RA, Rivera YS, et al. Increased expression of the RBPMS splice variants inhibits cell proliferation in ovarian cancer cells[J].Int J Mol Sci, 2022, 23: 14742.doi:10.3390/ijms232314742.
[9] Van Galen P, Hovestadt V, Wadsworth Ii MH, et al.Single-cell RNA-seq reveals AML hierarchies relevant to disease progression and immunity[J].Cell,2019,176:1265-1281.doi:10.1016/j.cell.2019.01.031.
[10] Papaemmanuil E, Gerstung M, Bullinger L, et al.Genomic classification and prognosis in acute myeloid leukemia[J].N Engl J Med,2016;374:2209-2221. doi:10.1056/NEJMoa1516192.
[11] Yokoyama A, Somervaille TCP, Smith KS, et al.The menin tumor suppressor protein is an essential oncogenic cofactor for MLL-associated leukemogenesis[J].Cell,2005,123:207-218. doi:10.1016/j.cell.2005.09.025.
[12] Meyer C, Schneider B, Jakob S, et al. The MLL recombinome of acute leukemias[J]. Leukemia, 2006, 20:777-784.doi:10.1038/sj.leu.2404150.
[13] Khurram SA, Whawell SA, Bingle L, et al.Functional expression of the chemokine receptor XCR1 on oral epithelial cells[J].J Pathol, 2010, 221:153-163.doi:10.1002/path.2695.
[14] Kim M, Rooper L, Xie J, et al.The lymphotactin receptor is expressed in epithelial ovarian carcinoma and contri-butes to cell migration and proliferation[J].Mol Cancer Res, 2012, 2012,10:1419-1429. doi:10.1158/1541-7786.MCR-12-0361.
[15] Wang T, Han S, Wu Z, et al. XCR1 promotes cell growth and migration and is correlated with bone metastasis in non-small cell lung cancer[J]. Biochem Biophys Res Commun, 2015, 464: 635-641.doi:10.1016/j.bbrc.2015.06.175.