Long non‐coding <scp>RNA </scp><i><scp>MALAT</scp>1</i> is an inducible stress response gene associated with extramedullary spread and poor prognosis of multiple myeloma

Handa, Hiroshi; Kuroda, Yuko; Kimura, Kei; Masuda, Yuta; Hattori, Hiroyuki; Alkebsi, Lobna; Matsumoto, Morio; Kasamatsu, Tetsuhiro; Kobayashi, Nobuhiko; Tahara, Kazukuni; Takizawa, Makiko; Koiso, Hiromi; Ishizaki, Takuma; Shimizu, Hiroaki; Yokohama, Akihiko; Tsukamoto, Norifumi; Saito, Takayuki; Murakami, Hirokazu

doi:10.1111/bjh.14882

Cited by 70 publications

(67 citation statements)

References 52 publications

(82 reference statements)

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“…Many studies have shown that lncRNAs are dysregulated in cancer and involved in oncogenic or tumor inhibitory processes (15). The aberrant lncRNAs expression including OIP5-AS1 (16), MALAT1 (17,18), MEG3 (19), CRNDE (20), H19 (21), UCA1 (22), and PACT1 (23) have been reported in MM. However, the investigation of lncRNA in MM is still in primary, and the understanding of their biological function needs to be progressively elucidated.…”

Section: Introductionmentioning

confidence: 99%

Retracted: Decreased expression of long noncoding RNA XLOC_013703 promotes cell growth via NF‐κB pathway in multiple myeloma

Huang

et al. 2019

IUBMB Life

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Long noncoding RNAs (lncRNAs) are dysregulated in cancer and involved in oncogenic or tumor inhibitory processes. The aim of the study was to investigate the expression pattern of lncRNA XLOC_013703 in multiple myeloma (MM) and to evaluate its biological role and potential significance. We found that XLOC_013703 was significantly decreased in CD138 positive plasma cells and serum of MM patients compared to normal controls, and the decreased XLOC_013703 expression was correlated with β2‐MG, serum‐free light chain (s‐FLC) and revised international staging system. RNA‐fluorescence in situ hybridization results revealed that XLOC_013703 was distributed both in the nucleus and in the cytoplasm of MM cells including H929, RPMI8226, and U266. Overexpression of XLOC_013703 inhibited the proliferation of U266 cells and blocked the cell cycle in G1 stage, thus contributing to MM cell apoptosis. By contrast, knockdown of XLOC_013703 promoted the growth of H929 cells. Western blot analysis confirmed that the expression of p‐IκBα and nuclear P65 was substantially increased in shRNA transfection groups compared to control groups, whereas overexpression of XLOC_013703 reduced these expressions. In conclusion, we confirmed that the decreased expression of a novel lncRNA, XLOC_013703, in MM. XLOC_013703 was involved in MM cell survival and proliferation via nuclear factor‐κB pathway which represents a potential therapeutic target for MM. © 2019 IUBMB Life, 71(9):1240–1251, 2019

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Section: Introductionmentioning

confidence: 99%

Retracted: Decreased expression of long noncoding RNA XLOC_013703 promotes cell growth via NF‐κB pathway in multiple myeloma

Huang

et al. 2019

IUBMB Life

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“…36,37 It is a poor prognostic factor in myeloma oncogenesis, and its expression increases with disease progression. [30][31][32] It is known that KDM3A promotes MALAT1 transcription by demethylating histones at its promoter region in neuroblastoma, and its upregulation could contribute to metastasis. 33 Furthermore, it has been shown that KDM3A-MALAT1-MAPK signaling contributes to cell proliferation in gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

“…These genes included those already known to act as oncogenes in myeloma, such as IGF1 and MAF (supplemental Table 5). Of the remaining candidate genes, the long noncoding RNA MALAT1 was of particular interest because it has been reported to be a poor prognostic factor in myeloma 30,31 and is involved in various antiapoptotic pathways in myeloma oncogenesis. 32 As expected, MALAT1 was upregulated during hypoxia in all 8 myeloma cell lines ( Figure 4B).…”

Section: Knockdown Of Kdm3a Induces Apoptosis In Myeloma Cells Under mentioning

confidence: 99%

Hypoxia-inducible KDM3A addiction in multiple myeloma

et al. 2018

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Key Points• Under hypoxia, KDM3A, but not IRF4, leads myeloma cells to acquire an antiapoptotic phenotype.• KDM3A regulates a long noncoding RNA, MALAT1, leading to upregulation of glycolytic genes under hypoxia.In multiple myeloma (MM), the bone marrow (BM) microenvironment may contain a myeloma cell fraction that has acquired treatment resistance by undergoing an epigenetic gene expression change. Hypoxic stress is an important factor in the BM microenvironment.Recently, we demonstrated that miR-210 was upregulated in hypoxia and downregulated IRF4, which is known as an essential factor in myeloma oncogenesis in normoxia. In the study, we demonstrated that myeloma cells still showed a strong antiapoptotic phenotype despite IRF4 downregulation, suggesting that another antiapoptotic factor might be involved under hypoxic stress. To determine the factor or factors, we conducted gene expression analysis on myeloma cells (primary samples and cell lines) that were exposed to chronic hypoxia and observed upregulation of glycolytic genes and genes encoding H3K9 demethylases in myeloma cells with hypoxia. Among these, KDM3A was most significantly upregulated in all examined cells, and its knockdown induced apoptosis of myeloma cells in chronic hypoxia.Expression of KDM3A was dependent on HIF-1a, which is a transcription factor specifically upregulated in hypoxia. We further demonstrated that an essential target of KDM3A was a noncoding gene, MALAT1, whose upregulation contributed to acquisition of an antiapoptotic phenotype by accumulation of HIF-1a, leading to upregulation of glycolytic genes under hypoxia. This process was independent from IRF4. These results led us to conclude that the hypoxia-inducible HIF-1a-KDM3A-MALAT1 axis also contributes to acquisition of the antiapoptotic phenotype via upregulation of glycolysis-promoting genes. Thus, this axis is a promising therapeutic target against myeloma cells in the BM microenvironment.

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“…This means that MALAT1 expression may serve as a molecular predictor for patients. Furthermore, MALAT1 expression was markedly higher in extramedullary myeloma (EMM), when compared to intramedullary myeloma cells . It was also found that MALAT1 expression level was positively correlated with the mRNA levels of HSP90, which has been reported to be induced by bortezomib, and contributes to drug resistance .…”

Section: Mechanisms Of Lncrnas In MMmentioning

confidence: 96%

The role of long non‐coding RNAs in multiple myeloma

Cui

Song

Fang

2019

European J of Haematology

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Multiple myeloma (MM) is still an incurable disease, and its pathogenesis involves cytogenetics and epigenetics. In recent years, the roles of long non‐coding RNAs (lncRNAs) in MM have been deeply studied by scholars. LncRNAs are defined as a class of non‐protein‐coding transcripts greater than 200 nucleotides in length, which are involved in a large spectrum of biological processes, including proliferation, differentiation, apoptosis, invasion, and chromatin remodeling. However, little is known about the specific mechanisms of these lncRNAs. They can act as oncogenic and/or tumor‐suppressive factors in the development and progression of MM. But that how do they work remains unclear. In this review, the recent progress in the study of functional lncRNAs associated with MM was summarized and the present knowledge about their expression and roles was discussed, to provide guidance for the in‐depth functional study of lncRNAs.

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Long non‐coding RNA MALAT1 is an inducible stress response gene associated with extramedullary spread and poor prognosis of multiple myeloma

Cited by 70 publications

References 52 publications

Retracted: Decreased expression of long noncoding RNA XLOC_013703 promotes cell growth via NF‐κB pathway in multiple myeloma

Retracted: Decreased expression of long noncoding RNA XLOC_013703 promotes cell growth via NF‐κB pathway in multiple myeloma

Hypoxia-inducible KDM3A addiction in multiple myeloma

The role of long non‐coding RNAs in multiple myeloma

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