HDAC1 Promotes the Migration of Human Myeloma cells Via Regulation of the LncRNA/Slug Axis

Overview

Journal Int J Mol Med

Specialty Genetics

Date 2021 Nov 5

PMID 34738621

Citations 1

Authors

Lisha Zheng

Ang Zhang

Jishan Liu

Min Liu

Yikun Zhang

Affiliations

Soon will be listed here.

Abstract

Understanding the mechanisms underlying malignancy in myeloma cells is important for targeted treatment and drug development. Histone deacetylases (HDACs) can regulate the progression of various cancer types; however, their roles in myeloma are not well known. In the present study, the expression of class I HDACs in myeloma cells and tissues was evaluated. Furthermore, the effects of HDAC1 on the migration of myeloma cells and the associated mechanisms were investigated. Among the class I HDACs evaluated, HDAC1 was upregulated in both myeloma cells and tissues. Targeted inhibition of HDAC1 suppressed the migration of myeloma cells. Of the assessed transcription factors, small interfering (si)‑HDAC1 decreased the expression of Slug. Overexpression of Slug reversed the si‑HDAC1‑mediated suppressed migration of myeloma cells. Mechanistically, the results revealed that HDAC1 regulated the mRNA stability of Slug, while it had no effect on its transcription or nuclear export. Furthermore, HDAC1 negatively regulated the expression of long non‑coding RNA (lncRNA) NONHSAT113026, which could bind with the 3'‑untranslated region of Slug mRNA to facilitate its degradation. The present study demonstrated that HDAC1 promoted the migration of human myeloma cells via regulation of lncRNA/Slug signaling.

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References

Ria R, Reale A, Vacca A . Novel agents and new therapeutic approaches for treatment of multiple myeloma. World J Methodol. 2014; 4(2):73-90. PMC: 4202483. DOI: 10.5662/wjm.v4.i2.73. View

Al Emran A, Marzese D, Ravindran Menon D, Stark M, Torrano J, Hammerlindl H . Distinct histone modifications denote early stress-induced drug tolerance in cancer. Oncotarget. 2018; 9(9):8206-8222. PMC: 5823586. DOI: 10.18632/oncotarget.23654. View

Garcia-Guerrero E, Gotz R, Doose S, Sauer M, Rodriguez-Gil A, Nerreter T . Upregulation of CD38 expression on multiple myeloma cells by novel HDAC6 inhibitors is a class effect and augments the efficacy of daratumumab. Leukemia. 2020; 35(1):201-214. PMC: 8318885. DOI: 10.1038/s41375-020-0840-y. View

Wang Z, Liu C . MiR-153 regulates metastases of gastric cancer through Snail. Tumour Biol. 2015; 37:15509–15515. DOI: 10.1007/s13277-015-3846-8. View

Quinn J, Chang H . Unique features of long non-coding RNA biogenesis and function. Nat Rev Genet. 2015; 17(1):47-62. DOI: 10.1038/nrg.2015.10. View

Chen Y, Zhao H, Li H, Feng X, Tang H, Qiu C . LINC01234/MicroRNA-31-5p/MAGEA3 Axis Mediates the Proliferation and Chemoresistance of Hepatocellular Carcinoma Cells. Mol Ther Nucleic Acids. 2019; 19:168-178. PMC: 6926330. DOI: 10.1016/j.omtn.2019.10.035. View

McCullough K, Hobbs M, Abeykoon J, Kapoor P . Common Adverse Effects of Novel Therapies for Multiple Myeloma (MM) and Their Management Strategies. Curr Hematol Malig Rep. 2018; 13(2):114-124. DOI: 10.1007/s11899-018-0443-0. View

Orlowski R . Why proteasome inhibitors cannot ERADicate multiple myeloma. Cancer Cell. 2013; 24(3):275-7. PMC: 3863636. DOI: 10.1016/j.ccr.2013.08.014. View

Brabletz T, Kalluri R, Nieto M, Weinberg R . EMT in cancer. Nat Rev Cancer. 2018; 18(2):128-134. DOI: 10.1038/nrc.2017.118. View

10.

Largo C, Saez B, Alvarez S, Suela J, Ferreira B, Blesa D . Multiple myeloma primary cells show a highly rearranged unbalanced genome with amplifications and homozygous deletions irrespective of the presence of immunoglobulin-related chromosome translocations. Haematologica. 2007; 92(6):795-802. DOI: 10.3324/haematol.11052. View

11.

Arienti C, Tesei A, Carloni S, Ulivi P, Romeo A, Ghigi G . SLUG silencing increases radiosensitivity of melanoma cells in vitro. Cell Oncol (Dordr). 2012; 36(2):131-9. DOI: 10.1007/s13402-012-0120-6. View

12.

Ye X, Brabletz T, Kang Y, Longmore G, Nieto M, Stanger B . Upholding a role for EMT in breast cancer metastasis. Nature. 2017; 547(7661):E1-E3. PMC: 6283276. DOI: 10.1038/nature22816. View

13.

Krumm A, Barckhausen C, Kucuk P, Tomaszowski K, Loquai C, Fahrer J . Enhanced Histone Deacetylase Activity in Malignant Melanoma Provokes RAD51 and FANCD2-Triggered Drug Resistance. Cancer Res. 2016; 76(10):3067-77. DOI: 10.1158/0008-5472.CAN-15-2680. View

14.

Barneda-Zahonero B, Parra M . Histone deacetylases and cancer. Mol Oncol. 2012; 6(6):579-89. PMC: 5528343. DOI: 10.1016/j.molonc.2012.07.003. View

15.

Wang Y, Shi J, Chai K, Ying X, Zhou B . The Role of Snail in EMT and Tumorigenesis. Curr Cancer Drug Targets. 2013; 13(9):963-972. PMC: 4004763. DOI: 10.2174/15680096113136660102. View

16.

Lin C, Wang L, Wang S, Chang Y, Wu Y, Chen H . Daxx inhibits hypoxia-induced lung cancer cell metastasis by suppressing the HIF-1α/HDAC1/Slug axis. Nat Commun. 2016; 7:13867. PMC: 5192219. DOI: 10.1038/ncomms13867. View

17.

Yeon M, Kim Y, Jung H, Jeoung D . Histone Deacetylase Inhibitors to Overcome Resistance to Targeted and Immuno Therapy in Metastatic Melanoma. Front Cell Dev Biol. 2020; 8:486. PMC: 7311641. DOI: 10.3389/fcell.2020.00486. View

18.

Tang Z, Ding S, Huang H, Luo P, Qing B, Zhang S . HDAC1 triggers the proliferation and migration of breast cancer cells via upregulation of interleukin-8. Biol Chem. 2017; 398(12):1347-1356. DOI: 10.1515/hsz-2017-0155. View

19.

Liang X, Deng M, Zhang C, Ping F, Wang H, Wang Y . Combined class I histone deacetylase and mTORC1/C2 inhibition suppresses the initiation and recurrence of oral squamous cell carcinomas by repressing SOX2. Cancer Lett. 2019; 454:108-119. DOI: 10.1016/j.canlet.2019.04.010. View

20.

Pu Y, Dong Z, Xia Y, Zhang M, Song J, Han J . LncRNA NONHSAT113026 represses renal cell carcinoma tumorigenesis through interacting with NF-κB/p50 and SLUG. Biomed Pharmacother. 2019; 118:109382. DOI: 10.1016/j.biopha.2019.109382. View