A Long Noncoding RNA Activated by TGF-β Promotes the Invasion-Metastasis Cascade in Hepatocellular Carcinoma

Yuan, Ji‐hang; Yang, Fusheng; Wang, Fang; Ma, Jinzhao; Guo, Yingjun; Tao, Qi-Fei; Liu, Feng; Pan, Wei; Wang, Tian; Zhou, Chuanchuan; Wang, Shaobing; Wang, Yu‐Zhao; Yang, Yuan; Yang, Ning; Zhou, Weiping; Yang, Guang-Shun; Sun, Shuhan

doi:10.1016/j.ccr.2014.03.010

Cited by 1,368 publications

(1,328 citation statements)

References 42 publications

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“…11,12,28 For example, lncRNA maternally expressed gene 3 (MEG3) has been found to inhibit liver fibrosis via p53. 11 In this study, HOTAIR was found to be upregulated in HSCs in vivo and in vitro during liver fibrosis.…”

Section: Discussionmentioning

confidence: 99%

“…10 Other ncRNAs, such as long intergenic non-coding RNAs (lincRNAs) and the heterogeneous group of long non-coding RNAs (lncRNAs), have also been reported to be involved in human diseases. [11][12][13] LncRNA is most commonly defined as a non-protein-coding RNA molecule longer than 200 nucleotides. Increasing evidence has demonstrated that lncRNAs are involved in a wide range of biological processes, including differentiation, proliferation, and apoptosis.…”

Section: Introductionmentioning

confidence: 99%

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HOTAIR Epigenetically Modulates PTEN Expression via MicroRNA-29b: A Novel Mechanism in Regulation of Liver Fibrosis

et al. 2017

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

HOTAIR Epigenetically Modulates PTEN Expression via MicroRNA-29b: A Novel Mechanism in Regulation of Liver Fibrosis

et al. 2017

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“…In this, it could be analogous to other ncRNAs, such as Linc-ROR, LncRNA-ATB, and MALAT1, which stabilize mRNAs by acting as competing endogenous RNAs to sequester miRNAs and inhibit the miRNA-mediated decay of their target mRNAs. [34][35][36] Alternatively, BC200 RNA may increase the stability of S100A11 mRNA by interacting with complementary sequences. There is a putative BC200 RNA binding site between positions ¡30 and ¡15 of S100A11 mRNA relative to the start codon (C 1 would be A of the ATG codon).…”

Section: Discussionmentioning

confidence: 99%

Knockdown of BC200 RNA expression reduces cell migration and invasion by destabilizing mRNA for calcium-binding protein S100A11

et al. 2017

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Although BC200 RNA is best known as a neuron-specific non-coding RNA, it is overexpressed in various cancer cells. BC200 RNA was recently shown to contribute to metastasis in several cancer cell lines, but the underlying mechanism was not understood in detail. To examine this mechanism, we knocked down BC200 RNA in cancer cells, which overexpress the RNA, and examined cell motility, profiling of ribosome footprints, and the correlation between cell motility changes and genes exhibiting altered ribosome profiles. We found that BC200 RNA knockdown reduced cell migration and invasion, suggesting that BC200 RNA promotes cell motility. Our ribosome profiling analysis identified 29 genes whose ribosomal occupations were altered more than 2-fold by BC200 RNA knockdown. Many (> 30%) of them were directly or indirectly related to cancer progression. Among them, we focused on S100A11 (which showed a reduced ribosome footprint) because its expression was previously shown to increase cellular motility. S100A11 was decreased at both the mRNA and protein levels following knockdown of BC200 RNA. An actinomycin-chase experiment showed that BC200 RNA knockdown significantly decreased the stability of the S100A11 mRNA without changing its transcription rate, suggesting that the downregulation of S100A11 was mainly caused by destabilization of its mRNA. Finally, we showed that the BC200 RNAknockdown-induced decrease in cell motility was mainly mediated by S100A11. Together, our results show that BC200 RNA promotes cell motility by stabilizing S100A11 transcripts.

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“…LncRNAs are very abundant with estimates of 430 000 lncRNAs transcripts in the human genome. [71][72][73][74][75][76][77] One group of investigators estimated that there were close to 60 000 lncRNAs including 8000 oncologic lncRNAs. 74 A growing number of these lncRNAs are being isolated and characterized from thyroid and other cancers.…”

Section: Non-coding Rnas and Emt Micrornas And Emtmentioning

confidence: 99%

The evolving concept of cancer stem-like cells in thyroid cancer and other solid tumors

Hardin

Zhang

Helein

et al. 2017

Laboratory Investigation

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The cancer stem-like cell (CSC) hypothesis postulates that a small population of cells in a cancer has self-renewal and clonal tumor initiation properties. These cells are responsible for tumor initiation, growth, recurrence and for resistance to chemotherapy and radiation therapy. CSCs can be characterized using markers such as SSEA-1, SSEA-4, CD44, CD24, ALDEFLUOR and others. CSCs form spheres when they are cultured in serum-free condition in low attachment plates and can generate tumors when injected into immune-deficient mice. During epithelial to mesenchymal transition (EMT), cells lose cellular adhesion and polarity and acquire an invasive phenotype. Recent studies have established a relationship between EMT and increased numbers of CSCs in some solid malignancies. Non-coding RNAs such as microRNAs and long non-coding RNAs (lncRNAs) have been shown to have important roles during EMT and some of these molecules also have regulatory roles in the proliferation of CSCs. Specific lncRNAs enhanced cell migration and invasion in breast carcinomas, which was associated with the generation of stem cell properties. The tumor microenvironment of CSCs also has an important role in tumor progression. Recent studies have shown that the interaction between tumor cells and the local microenvironment at the metastatic site leads to the development of premetastatic niche(s) and allows for the proliferation of the metastatic cells during colonization. The role of exosomes in the microenvironment during the EMT program is currently a major area of research. This review examines CSCs and the relationship between EMT and CSCs in solid tumors with emphasis on thyroid CSCs. The role of non-coding RNAs and of the microenvironment in EMT and in tumor progression are also examined. This review also highlights the growing number of studies that show the close association of EMT and CSCs and the role of exosomes and other elements of the tissue microenvironment in CSC metastasis. A better understanding of these mechanisms will lead to more effective targeting of primary and metastatic malignancies.

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A Long Noncoding RNA Activated by TGF-β Promotes the Invasion-Metastasis Cascade in Hepatocellular Carcinoma

Cited by 1,368 publications

References 42 publications

HOTAIR Epigenetically Modulates PTEN Expression via MicroRNA-29b: A Novel Mechanism in Regulation of Liver Fibrosis

HOTAIR Epigenetically Modulates PTEN Expression via MicroRNA-29b: A Novel Mechanism in Regulation of Liver Fibrosis

Knockdown of BC200 RNA expression reduces cell migration and invasion by destabilizing mRNA for calcium-binding protein S100A11

The evolving concept of cancer stem-like cells in thyroid cancer and other solid tumors

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