Long Noncoding RNA MALAT1 Promotes Hepatocellular Carcinoma Development by SRSF1 Upregulation and mTOR Activation

Malakar, Pushkar; Shilo, Asaf; Mogilevsky, Adi; Stein, Ilan; Pikarsky, Eli; Nevo, Yuval; Benyamini, Hadar; Elgavish, Sharona; Zong, Xinying; Prasanth, Kannanganattu V.; Karni, Rotem

doi:10.1158/0008-5472.can-16-1508

Cited by 256 publications

(243 citation statements)

References 55 publications

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“…Evidence suggests that MALAT1 may act like an oncogene in several malignancies, including lung cancer [17, 24], pancreatic cancer [19], liver cancer [20], bladder cancer [25], prostate cancer[26], colon cancer [27, 28], renal cell carcinoma [18], and oral squamous cell carcinomas [29, 30]. Lowering MALAT1 expression in hepatocellular carcinoma cells resulted in reduced cell proliferation and colony formation [20]. MALAT1 was also found to promote colon cancer cell proliferation, invasion and metastasis in vitro and in vivo by increasing AKAP-9 expression [28].…”

Section: Discussionmentioning

confidence: 99%

“…MALAT1 is localized to nuclear speckles, and regulates messenger RNA splicing by interaction with SR proteins and splicing factors [14–16]. MALAT1 expression is upregulated in several solid tumors, including the breast, pancreas, lung, colon, prostate and liver [11], and is suspected to be involved in tumorigenesis or disease progression [17–20]. In the present study, we analyzed MALAT1 expression in breast cancer and investigated its associations with clinical and pathological features and patient survival.…”

Section: Introductionmentioning

confidence: 99%

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High expression of long non-coding RNA MALAT1 in breast cancer is associated with poor relapse-free survival

Wang

Katsaros²,

Biglia³

et al. 2018

Breast Cancer Res Treat

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

High expression of long non-coding RNA MALAT1 in breast cancer is associated with poor relapse-free survival

Wang

Katsaros²,

Biglia³

et al. 2018

Breast Cancer Res Treat

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“…Lu et al32 reported that MYC stimulates the transcription of DANCR, and inhibition of DANCR impairs cell proliferation which could be partially rescued by p21 silencing in human ovarian cancer. In addition, lncRNA MALAT1 is upregulated in hepatocellular carcinoma and exerts oncogenic function through activating Wnt pathway by induction of splicing factor SRSF1 33. Besides, antisense lncRNA EZR‐AS1 promotes the mobility and invasiveness of ESCC cells through enhancing SMYD3‐dependent H3K4 methylation and transcription of the EZR gene 34.…”

Section: Discussionmentioning

confidence: 99%

A genome‐wide analysis of long noncoding RNA profile identifies differentially expressed lncRNAs associated with Esophageal cancer

et al. 2018

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Esophageal cancer is one of the most common cancers and a leading cause of cancer‐related death worldwide. However, the mechanism of esophageal cancer pathogenesis remains poorly understood. Long noncoding RNAs (lncRNAs) dysregulation have been reported to involve in various human cancers, which highlights the potential of lncRNAs used as novel biomarkers for cancer diagnosis. Although more efforts have been made to identify novel lncRNAs signature in esophageal cancer, the expression pattern, prognostic value, and biological function of most lncRNAs in esophageal cancer still need to be systematically investigated. In this study, we comprehensively analyzed the expression profile of lncRNAs in more than 200 esophageal cancer patients tissue samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). We identified thousands of lncRNAs are differentially expressed in esophageal cancer tissues, and many of those lncRNAs expression are associated with patients overall survival or recurrence‐free survival time. Moreover, copy number variation analyses revealed that genomic loci copy number amplification or deletion might contribute to these lncRNAs dysregulation. Among these lncRNAs, DUXAP8 and LINC00460 were significantly upregulated, and GO enrichment analyses indicated that the two lncRNAs associated protein‐coding genes involve with many known biological processes, such as cell cycle and cell‐cell adherens junction. Further experimental validation revealed that knockdown of DUXAP8 could impair esophageal cancer cells proliferation and invasion in vitro. Taken together, our findings identified more aberrantly expressed lncRNAs in esophageal cancer that may provide a useful resource for identifying novel esophageal cancer associated lncRNAs.

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“…Zhao et al (27) revealed that SNHG5/miR-32 axis regulated cell proliferation and migration of gastric cancer by targeting KLF4. Malakar et al (28) demonstrated that long noncoding RNA MALAT1 promoted hepatocellular carcinoma development by upregulating SRSF1 and activating mTOR. As for CRC, plenty well-studied lncRNAs have been reported to be dysregulated in CRC tissues and participate in CRC progression via multiple mechanisms (29)(30)(31).…”

Section: Discussionmentioning

confidence: 99%

lncRNA FAM83H‑AS1 is associated with the prognosis of colorectal carcinoma and promotes cell proliferation by targeting the Notch signaling pathway

et al. 2017

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Abstract. The long non-coding RNA, FAM83H antisense RNA 1 (head to head) (FAM83H-AS1), has exhibited a functional role as an oncogene in a number of different types of cancer. The aim of the present study was to reveal the dysregulation of FAM83H-AS1 in colorectal carcinoma (CRC) samples and elucidate its underlying associations with the Notch signaling pathway. The expression profiles of FAM83H-AS1 and two Notch signaling-associated molecules, Notch1 and Hes family basic-helix-loop-helix transcription factor 1 (Hes1), were measured by reverse transcription-polymerase chain reaction and western blot analysis. The Pearson χ 2 test was employed to evaluate the associations between FAM83H-AS1 expression and clinical features. A statistically significant positive association between the expression levels of FAM83H-AS1 and those of Notch1 or Hes1 in CRC tissues was analyzed by Spearman's correlation analysis. The Kaplan-Meier method was used to compare the overall survival curves between the highly-expressed and low-expressed FAM83H-AS1 groups via a log-rank test. Specific small hairpin RNA was transfected to silence endogenous FAM83H-AS1. MTT and colony formation assays were performed to measure the growth-inhibition effect of silenced FAM83H-AS1. The levels of FAM83H-AS1, Notch1 and Hes1 were significantly increased in CRC samples and cell lines. Cell proliferation was markedly inhibited when FAM83H-AS1 was knocked down and this effect mediated by FAM83H-AS1 could be reversed by Notch1 regulators. Thus, downregulated FAM83H-AS1 exhibited an anti-proliferative role in CRC by repressing the Notch signaling pathway.

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Long Noncoding RNA MALAT1 Promotes Hepatocellular Carcinoma Development by SRSF1 Upregulation and mTOR Activation

Cited by 256 publications

References 55 publications

High expression of long non-coding RNA MALAT1 in breast cancer is associated with poor relapse-free survival

High expression of long non-coding RNA MALAT1 in breast cancer is associated with poor relapse-free survival

A genome‐wide analysis of long noncoding RNA profile identifies differentially expressed lncRNAs associated with Esophageal cancer

lncRNA FAM83H‑AS1 is associated with the prognosis of colorectal carcinoma and promotes cell proliferation by targeting the Notch signaling pathway

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