Long noncoding RNAs in cancer: mechanisms of action and technological advancements

Bartoniček, Nenad; Mååg, Jesper L.V.; Dinger, Marcel E.

doi:10.1186/s12943-016-0530-6

Cited by 384 publications

(298 citation statements)

References 148 publications

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“…Over the past few decades, despite numerous efforts to improve the survival of patients with gastric cancer, such as improved living standards, a reduction in chronic Helicobacter pylori infections, and remarkable advances in diagnosis and treatment, the 5-year overall survival rate of patients with gastric cancer is still lower than 30%, due to the late advanced stage at which it is diagnosed and the high incidence of tumor metastasis and recurrence [3,4]. Therefore, there are still considerable clinical challenges regarding how to detect this malignancy early and to improve its prognosis.…”

Section: Introductionmentioning

confidence: 99%

Long Non-Coding RNA RP11-789C1.1 Suppresses Epithelial to Mesenchymal Transition in Gastric Cancer Through the RP11-789C1.1/MiR-5003/E-Cadherin Axis

Wu¹,

Huang²,

Peng³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Gastric cancer (GC) is a common malignancy with a global incidence that ranks fourth among all tumor types. Epithelial-to-mesenchymal transition (EMT) is a tumor biological process with a role in GC cell metastasis. Long non-coding RNAs (lncRNAs) and microRNAs possess important regulatory functions at the cellular level and in diverse pathophysiological processes. This study was conducted to investigate whether lncRNA RP11-789C1.1 regulates EMT in GC by mediating the miR-5003/E-cadherin pathway. Methods: RP11-789C1.1 and miR-5003 expression was detected in GC specimens and cell lines by quantitative real-time PCR. Western blotting and immunohistochemistry were performed to detect EMT markers in GC. Cell Counting Kit 8 assays were carried out to explore cell proliferation. Wound healing and Transwell assays were conducted to determine the migration and invasion of GC cells. To clarify the correlation between RP11-789C1.1, miR-5003, and E-cadherin, dual-luciferase reporter assays were applied. Results: LncRNA RP11-789C1.1 was significantly down-regulated in GC patients and cell lines, along with the concomitant up-regulation of miR-5003. Silencing RP11-789C1.1 and over-expressing miR-5003 significantly promoted the tumor behavior of GC cells. Dual-luciferase reporter assays confirmed that miR-5003 was the target of both RP11-789C1.1 and E-cadherin. Furthermore, at both the mRNA and protein level, silencing RP11-789C1.1 remarkably reduced the expression of E-cadherin and promoted EMT, which were reversed by knocking down miR-5003. Conclusions: LncRNA RP11-789C1.1 inhibited EMT in GC through the RP11-789C1.1/miR-5003/E-cadherin axis, which could be a promising therapeutic target for GC.

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Section: Introductionmentioning

confidence: 99%

Long Non-Coding RNA RP11-789C1.1 Suppresses Epithelial to Mesenchymal Transition in Gastric Cancer Through the RP11-789C1.1/MiR-5003/E-Cadherin Axis

Wu¹,

Huang²,

Peng³

et al. 2018

Cell Physiol Biochem

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“…7 Among them, lncRNAs have acquired extensive attention, recently, as new regulators in many biological processes, such as transcriptional regulation, 8 differentiation, 9 immune response, 10 metabolism, 11 cell growth, and especially tumorigenesis. 12,13 Moreover, since an increasing number of reports have indicated that their abnormal expression is frequently observed in human cancers, some lncRNAs have been validated as biomarkers for diagnostic, metastasis, recurrence, and poor prognosis, [14][15][16][17] such as MALAT-1 for lung, glioma, gastric, and prostate cancer; [18][19][20][21] HOTAIR for breast, ovarian, pancreatic, and colorectal cancer; [22][23][24][25] and CCAT2 for oral squamous cell carcinoma and bladder cancer. 26,27 Zinc finger antisense 1 (ZFAS1) locus is host to three C/D-box small nucleolar RNAs (snoRNAs), and its transcription initiates from the antisense strand near the 5′ end of the protein-coding gene Znfx1.…”

Section: Introductionmentioning

confidence: 99%

Upregulation of long noncoding RNA zinc finger antisense 1 enhances epithelial–mesenchymal transition in vitro and predicts poor prognosis in glioma

Chen

Zhang

et al. 2017

Tumour Biol.

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Increasing evidence indicates that long noncoding RNAs play important roles in development and progression of various cancers. Zinc finger antisense 1 is a novel long noncoding RNA whose clinical significance, biological function, and underlying mechanism are still undetermined in glioma. In this study, we reported that zinc finger antisense 1 expression was markedly upregulated in glioma and tightly correlated with clinical stage. Moreover, patients with high zinc finger antisense 1 expression had shorter survival. Multivariate Cox regression analysis provided a clue that, probably, zinc finger antisense 1 level could serve as an independent prognostic factor for glioma. Functionally, zinc finger antisense 1 acted as an oncogene in glioma because its knockdown could promote apoptosis and significantly inhibit cell proliferation, migration, and invasion. Furthermore, zinc finger antisense 1 silencing could result in cell cycle arrest at the G0/G1 phase and correspondingly decrease the percentage of S phase cells in both U87 and U251 cell lines. Moreover, it was found that silenced zinc finger antisense 1 could impair migration and invasion by inhibiting the epithelial-mesenchymal transition through reducing the expression of MMP2, MMP9, N-cadherin, Integrin β1, ZEB1, Twist, and Snail as well as increasing E-cadherin level in glioma. Taken together, our data identified that zinc finger antisense 1 might act as a valuable prognostic biomarker and potential therapeutic target for glioma.

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“…By regulating gene expression, lncRNAs play crucial roles in multiple biological processes such as development, differentiation and carcinogenesis [8][9][10][11]. Specific lncRNAs are correlated with fibrotic disorders including hypertrophic scar [12], keloid [13], and lung fibrosis [14], indicating that lncRNAs may be involved in imbalances in ECM deposition.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of LncRNA AC067945.2 Down-Regulates Collagen Expression in Skin Fibroblasts and Possibly Correlates with the VEGF and Wnt Signalling Pathways

Chen¹,

Li²,

Li³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Long non-coding RNAs (lncRNAs) are thought to play crucial roles in human diseases. However, the function of lncRNAs in hypertrophic scar formation remains poorly understood. Methods: Utilizing qRT-PCR, we explored the expression changes of AC067945.2. Overexpression of AC067945.2 in normal skin fibroblasts was performed by transient plasmid transfection. Western blot was used to check the proteins' expression changes. Cell Counting Kit-8 (CCK-8) assay and Annexin V/7-AAD staining were used to examine cell proliferation and apoptosis, respectively. mRNA-seq was applied to dissect the differentially expressed mRNAs in AC067945.2 overexpressed cells. We also performed ELISA to detect the VEGF secretion. Results: AC067945.2 was down-regulated in hypertrophic scar tissues. Overexpression of AC067945.2 did not affect cell proliferation, but it mildly promoted early apoptosis in normal skin fibroblasts. Furthermore, AC067945.2 overexpression inhibited the expression of COL1A1, COL1A2, COL3A1 and α-SMA proteins. Transforming growth factor-β1 (TGF-β1) could inhibit the expression of AC067945.2. Based on mRNA-seq data, compared with mRNAs in the control group, 138 mRNAs were differentially expressed, including 14 upregulated and 124 down-regulated transcripts, in the AC067945.2 overexpression group. Gene ontology and pathway analyses revealed that AC067945.2 overexpression was correlated with developmental processes, binding, extracellular region, and the vascular endothelial

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Long noncoding RNAs in cancer: mechanisms of action and technological advancements

Cited by 384 publications

References 148 publications

Long Non-Coding RNA RP11-789C1.1 Suppresses Epithelial to Mesenchymal Transition in Gastric Cancer Through the RP11-789C1.1/MiR-5003/E-Cadherin Axis

Long Non-Coding RNA RP11-789C1.1 Suppresses Epithelial to Mesenchymal Transition in Gastric Cancer Through the RP11-789C1.1/MiR-5003/E-Cadherin Axis

Upregulation of long noncoding RNA zinc finger antisense 1 enhances epithelial–mesenchymal transition in vitro and predicts poor prognosis in glioma

Overexpression of LncRNA AC067945.2 Down-Regulates Collagen Expression in Skin Fibroblasts and Possibly Correlates with the VEGF and Wnt Signalling Pathways

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