Gene expression profiling and in vitro functional studies reveal RAD54L as a potential therapeutic target in multiple myeloma

Bong, Ivyna Pau Ni and Ng, Ching Ching and Othman, Norodiyah and Esa, Ezalia (2022) Gene expression profiling and in vitro functional studies reveal RAD54L as a potential therapeutic target in multiple myeloma. Genes & Genomics, 44 (8). 957 -966. ISSN 1976-9571, DOI

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Background: Current advances in the molecular biology of multiple myeloma (MM) are not sufficient to fully delineate the genesis and development of this disease. Objective: This study aimed to identify molecular targets underlying MM pathogenesis. Methods: mRNA expression profiling for 29 samples (19 MM samples, 7 MM cell lines and 3 controls) were obtained using microarray. We evaluated the in vitro effects of RAD54L gene silencing on the proliferation, apoptosis and cell cycle distribution in KMS-28BM human MM cells using siRNA approach. Cell proliferation was determined by MTS assay while apoptosis and cell cycle distribution were analysed with flow cytometry. Gene and protein expression was evaluated using RT-qPCR and ELISA, respectively. Results: Microarray results revealed a total of 5124 differentially expressed genes (DEGs), in which 2696 and 2428 genes were up-regulated and down-regulated in MM compared to the normal controls, respectively (fold change ≥ 2.0; P < 0.05). Up-regulated genes (RAD54L, DIAPH3, SHCBP1, SKA3 and ANLN) and down-regulated genes (HKDC1, RASGRF2, CYSLTR2) have never been reported in association with MM. Up-regulation of RAD54L was further verified by RT-qPCR (P < 0.001). In vitro functional studies revealed that RAD54L gene silencing significantly induced growth inhibition, apoptosis (small changes) and cell cycle arrest in G0/G1 phase in KMS-28BM (P < 0.05). Silencing of RAD54L also decreased its protein level (P < 0.05). Conclusions: This study has identified possible molecular targets underlying the pathogenesis of MM. For the first time, we reveal RAD54L as a potential therapeutic target in MM, possibly functioning in the cell cycle and checkpoint control. © 2022, The Author(s).

Item Type: Article
Funders: Ministry of Health Malaysia [Grant No:NMRR-18-729-41414]
Uncontrolled Keywords: Cell cycle proteins; Cell line, tumor; Cell proliferation; DNA helicases; DNA-binding proteins; Gene expression Profiling; Gene Silencing; Humans; Microtubule-Associated Proteins; Multiple Myeloma; Shc Signaling Adaptor Proteins; messenger RNA; Rad54 protein; Shc signaling adaptor protein; small interfering RNA; cell cycle protein; DNA binding protein; DNA helicase; microtubule associated protein; RAD54L protein, human; Shc signaling adaptor protein; SHCBP1 protein, human; Ska3 protein, human; adult; aged; apoptosis; Article; cell cycle; cell cycle arrest; cell cycle G1 phase; cell proliferation; clinical article; controlled study; differential gene expression; down regulation; enzyme linked immunosorbent assay; female; flow cytometry; G1 phase cell cycle checkpoint; gene expression profiling; gene silencing; growth inhibition; human; human cell; IM-9 cell line; in vitro study; male; microarray analysis; MM1.S cell line; MTS assay; multiple myeloma; multiple myeloma cell line; pathogenesis; real time polymerase chain reaction; RPMI-8226 cell line; tumor gene; U266B1 cell line; upregulation; gene expression profiling; genetics; metabolism; multiple myeloma; procedures; tumor cell line
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculty of Science > Institute of Biological Sciences
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 23 Oct 2023 03:50
Last Modified: 23 Oct 2023 03:50

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