NORAD promotes multiple myeloma cell progression via BMP6/P-ERK1/2 axis

Ma, Tao; Chen, Yan; Yi, Zhigang; Liu, Jia; Li, Yanhong; Bai, Jun; Tie, Wenting; Huang, Mei; Zhu, Xiaofeng; Wang, Ji; Du, Juan; Zuo, Xiu-Qin; Li, Qin; Lin, Fan-Li; Liu, Tang; Guo, Jing; Xiao, Hong-Wen; Liu, Qian; Ma, Xiaoli; Li, Lijuan; Zhang, Liansheng

doi:10.1016/j.cellsig.2022.110474

Cited by 5 publications

(8 citation statements)

References 33 publications

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“…NDMM, PTMM and HD did not differ in general information such as age and gender. The patients' bone marrow was handled in a manner consistent with our previous study ( 21 ). Briefly, mononuclear cells were isolated from the bone marrow of MM patients and HD by density gradient centrifugation and stored in a −80°C refrigerator (Haier, China, DW-86L728J) after adding 1 mL of Trizol reagent (TIANGEN, China, DP424).…”

Section: Methodsmentioning

confidence: 99%

“…The methods, reagents and instruments for RNA extraction and qPCR were the same as in our previous study ( 21 ). Briefly, total RNA is isolated using Trizol, reverse transcribed into cDNA, primers are added and detected using the ThermoFisher 7500 real time PCR system.…”

Section: Methodsmentioning

confidence: 99%

“…SiRNA targeting LAMP5 (SiLAMP5) and siRNA negative control (SiNC) were acquired from Genepharma (Shanghai, China). Briefly, 3 × 10 5 cells were plated in 6-well plates, and Lipofectamine 2000 (Invitrogen) was used for siRNA transfection (21) . After 24 h of transfection, the medium was replaced, flow cytometry was performed after 48 h of transfection, and western blot was performed after 72 h of transfection.…”

Section: Methodsmentioning

confidence: 99%

“…Cells were collected 48 h after transfection and washed once with phosphate buffer saline (PBS). Cell suspension was mixed with 5 μL Annexin V-APC and 10 μL 7-AAD (Multi sciences, China, AP105) for 15 min in a dark room ( 21 ). Then apoptotic cells were detected by flow cytometry (Cytoflex, Beckman Coulter, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Cells were collected 48 h after transfection and washed once with cold PBS, then resuspended and fixed with 70% cold ethanol in 4°C overnight. The cells were washed again with cold PBS, stained with a mixture of 1 mL PI and RNase A (Multi sciences, China, CCS012), and incubated in darkness at room temperature for 30 min ( 21 ). Then cell cycle was analyzed by flow cytometry (Cytoflex, Beckman Coulter, USA).…”

Section: Methodsmentioning

confidence: 99%

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LAMP5 may promote MM progression by activating p38

Chen¹,

Ma²

2023

Pathol. Oncol. Res.

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Multiple myeloma (MM) is the second most common tumor of the hematologic system. MM remains incurable at this time. In this study, we used bioinformatics analysis to find key genes in the pathogenesis of MM. We first found that Lysosome associated membrane protein 5 (LAMP5) expression was sequentially increased in healthy donors (HD), monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM) and newly diagnosed MM (NDMM), relapsed MM (RMM). We collected bone marrow from patients with NDMM, HD and post-treatment MM (PTMM) and performed qPCR analysis of LAMP5, and found that the expression of LAMP5 is stronger in NDMM than in HD, and decreases after treatment. Western blotting assay also found more expression of LAMP5 in NDMM than in HD. Patients with high LAMP5 expression have a higher DS (Durie-Salmon) stage and worse prognosis. We next verified the expression of LAMP5 in four MM cell lines and silenced LAMP5 expression in RPMI-8226 and AMO-1, and explored the effects of LAMP5 silencing on MM cell apoptosis and cell cycle by flow cytometry and western blotting. Knockdown of LAMP5 promoted apoptosis in MM cells, but had no effect on the cell cycle. Mechanistically, LAMP5 may exert its pro-tumor effects in MM in part through activation of p38 protein. We screened LAMP5 for the first time as a key gene for MM progression and recurrence, and found that LAMP5 may exert its pro-tumor effects in MM through activation of p38 protein.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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LAMP5 may promote MM progression by activating p38

Chen¹,

Ma²

2023

Pathol. Oncol. Res.

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LGR4 promotes tumorigenesis by activating TGF-β1/Smad signaling pathway in multiple myeloma

Liu

et al. 2023

Cellular Signalling

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MALAT1 regulates network of microRNA-15a/16–VEGFA to promote tumorigenesis and angiogenesis in multiple myeloma

Yan,

Gao,

et al. 2023

Carcinogenesis

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MALAT1 is one of the most hopeful members implicated in angiogenesis in a variety of non-malignant diseases. In multiple myeloma (MM), MALAT1 is recognized as the most highly expressed lncRNA. However, the functional roles of MALAT1 in angiogenesis and the responsible mechanisms have not yet been explored. Herein, we discovered a novel regulatory network dependent on MALAT1 in relation to MM tumorigenesis and angiogenesis. We observed that MALAT1 was upregulated in MM and significantly associated with poor overall survival. MALAT1 knockdown suppressed MM cell proliferation and promoted apoptosis, while restricting endothelial cells angiogenesis. Moreover, MALAT1 directly targeted microRNA-15a/16, and microRNA-15a/16 suppression partly reverted the effects of MALAT1 deletion on MM cells in vitro as well as tumor growth and angiogenesis in vivo. In addition, further study indicated that MALAT1 functioned as a competing endogenous RNA (ceRNA) for microRNA-15a/16 to regulate VEGFA expression. Our results suggest that MALAT1 plays an important role in the regulatory axis of microRNA-15a/16-VEGFA to promote tumorigenicity and angiogenesis in MM. Consequently, MALAT1 could serve as a novel promising biomarker and a potential antiangiogenic target against MM.

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NORAD promotes multiple myeloma cell progression via BMP6/P-ERK1/2 axis

Cited by 5 publications

References 33 publications

LAMP5 may promote MM progression by activating p38

LAMP5 may promote MM progression by activating p38

LGR4 promotes tumorigenesis by activating TGF-β1/Smad signaling pathway in multiple myeloma

MALAT1 regulates network of microRNA-15a/16–VEGFA to promote tumorigenesis and angiogenesis in multiple myeloma

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