MALAT1 long non-coding RNA is overexpressed in multiple myeloma and may serve as a marker to predict disease progression

Abstract

BackgroundThe pathogenesis of multiple myeloma involves complex genetic and epigenetic events. This study aimed to investigate the role and clinical relevance of the long non-coding RNA (lncRNA), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in multiple myeloma.MethodsBone marrow mononuclear cells were collected for analysis. The samples of multiple myeloma were taken from 45 patients at diagnosis, 61 post-treatment, and 18 who relapsed or had progression. Control samples were collected from 20 healthy individuals. Real-time quantitative reverse transcription polymerase chain reactions were performed to evaluate the expression of MALAT1. The clinical relevance of MALAT1 expression was also explored.ResultsMALAT1 was overexpressed in the newly diagnosed patients compared with post-treatment patients (mean ∆CT: -5.54 ± 0.16 vs. -3.84 ± 0.09, 3.25-fold change; p < 0.001) and healthy individuals (mean ∆CT: -5.54 ± 0.16 vs. -3.95 ± 0.21, 3.01-fold change; p < 0.001). The expression of MALAT1 strongly correlated with disease status, and the magnitude of change in MALAT1 post-treatment had prognostic relevance. The patients with early progression had a significantly smaller change in MALAT1 after treatment (mean ∆CT change: 1.26 ± 1.06 vs. 2.09 ± 0.79, p = 0.011). A cut-off value of the change in MALAT1 (∆CT change: 1.5) was obtained, and the patients with a greater decrease in MALAT1 (difference in ∆CT >1.5) had significantly longer progression-free survival compared with the patients with a smaller MALAT1 change (24 months vs. 11 months; p = 0.001). For the post-treatment patients, the risk of early progression could be predicted using this cut-off value.ConclusionsMALAT1 was overexpressed in patients with myeloma and may play a role in its pathogenesis. In addition, MALAT1 may serve as a molecular predictor of early progression.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-809) contains supplementary material, which is available to authorized users.

MALAT1 functions as a competing endogenous RNA to mediate Rac1 expression by sequestering miR-101b in liver fibrosis

“…21,22 Finally, the high level of MALAT1 can act as a marker to predict disease progression in colorectal cancer, multiple myeloma, pancreatic cancer, and non-small cell lung cancer. [23][24][25][26] However, to the best of our knowledge, the biological role and underlying mechanism of MALAT1 in liver fibrosis has not been reported.…”

Hypoxia-inducible KDM3A addiction in multiple myeloma

“…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.…”

“…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).…”

Prognostic significance of long non-coding RNA MALAT-1 in various human carcinomas: a meta-analysis

“…Furthermore, eight potentially suitable works were excluded as they lacked sufficient survival data (HRs and survival curves) for analysis. Therefore, 12 eligible articles were included in this meta-analysis (Ji et al, 2003;Schmidt et al, 2011;Lai et al, 2012;Cho et al, 2014;Liu et al, 2014;Okugawa et al, 2014;Zheng et al, 2014;Hirata et al, 2015;Ma et al, 2015;Pang et al, 2015;Shen et al, 2015;Zhang et al, 2015). The main features and results of the eligible articles are summarized in Tables 1 and 2.…”