Global Positioning System: Understanding Long Noncoding RNAs through Subcellular Localization

Carlevaro-Fita, Joana; Johnson, Rory

doi:10.1016/j.molcel.2019.02.008

Cited by 234 publications

(168 citation statements)

References 178 publications

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“…The function of lncRNA depends mainly on its subcellular localization. 21 Here, by performing nuclear-cytoplasmic fractionation and FISH assays, we found that ARAP1-AS1 was predominately located in the nucleus in CC cells. Given that nuclear lncRNA regulated gene expression mainly via formation of functional lncRNA-protein complexes, 12 we then used in silico prediction combined with pull-down assay to identify ARAP1-AS1-binding proteins, and found that ARAP1-AS1 was able to directly bind to PSF.…”

Section: Discussionmentioning

confidence: 74%

Retracted: Long non‐coding RNA ARAP1‐AS1 promotes tumorigenesis and metastasis through facilitating proto‐oncogene c‐Myc translation via dissociating PSF/PTB dimer in cervical cancer

Zhang

Wang

2020

Cancer Medicine

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Long non‐coding RNA (lncRNA) is emerging as a pivotal regulator in tumorigenesis and aggressive progression. Here, we focused on an oncogenic lncRNA, ARAP1 antisense RNA 1 (ARAP1‐AS1), which was notably upregulated in cervical cancer (CC) tissues, cell lines and serum. High ARAP1‐AS1 expression was closely associated with larger tumor size, advanced FIGO stage as well as lymph node metastasis. Importantly, it was identified as an effective diagnostic and prognostic biomarker for CC. In vitro and in vivo assays showed that knockdown of ARAP1‐AS1 inhibited, while overexpression of ARAP1‐AS1 promoted CC cell growth and dissemination. Stepwise mechanistic dissection unveiled that ARAP1‐AS1 could directly interact with PSF to release PTB, resulting in accelerating the internal ribosome entry site (IRES)‐driven translation of proto‐oncogene c‐Myc, thereby facilitating CC development and progression. Moreover, c‐Myc was able to transcriptionally activate ARAP1‐AS1 by directly binding to the E‐box motif located on ARAP1‐AS1 promoter. Taken together, our findings clearly reveal the crucial role of ARAP1‐AS1 in CC tumorigenesis and metastasis via regulation of c‐Myc translation, targeting ARAP1‐AS1 and its related regulatory loop implicates the therapeutic possibility for CC patients.

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Section: Discussionmentioning

confidence: 74%

Retracted: Long non‐coding RNA ARAP1‐AS1 promotes tumorigenesis and metastasis through facilitating proto‐oncogene c‐Myc translation via dissociating PSF/PTB dimer in cervical cancer

Zhang

Wang

2020

Cancer Medicine

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“…The molecular functions of lncRNAs are primarily determined by their subcellular localization [41]. Thus, to further unravel the downstream effects of SNHG12, we analyzed the localization of SNHG12 in TMZ-resistant cells.…”

Section: Discussionmentioning

confidence: 99%

DNA-methylation-mediated activating of lncRNA SNHG12 promotes temozolomide resistance in glioblastoma

et al. 2020

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Background: Accumulating evidence shows that long noncoding RNAs (lncRNAs) are important regulator molecules involved in diverse biological processes. Acquired drug resistance is a major challenge in the clinical treatment of glioblastoma (GBM), and lncRNAs have been shown to play a role in chemotherapy resistance. However, the underlying mechanisms by which lncRNA mediates TMZ resistance in GBM remain poorly characterized. Methods: Quantitative reverse transcription PCR (qRT-PCR) and fluorescence in situ hybridization assays were used to detect small nucleolar RNA host gene 12 (SNHG12) levels in TMZ-sensitive and TMZ-resistant GBM cells and tissues. The effects of SNHG12 on TMZ resistance were investigated through in vitro assays (western blots, colony formation assays, flow cytometry assays, and TUNEL assays). The mechanism mediating the high expression of SNHG12 in TMZ-resistant cells and its relationships with miR-129-5p, mitogen-activated protein kinase 1 (MAPK1), and E2F transcription factor 7 (E2F7) were determined by bioinformatic analysis, bisulfite amplicon sequencing, methylation-specific PCR, dual luciferase reporter assays, chromatin immunoprecipitation assays, RNA immunoprecipitation assays, immunofluorescence, qRT-PCR, and western blot. For in vivo experiments, an intracranial xenograft tumor mouse model was used to investigate SNHG12 function. Results: SNHG12 was upregulated in TMZ-resistant cells and tissues. Overexpression of SNHG12 led to the development of acquired TMZ resistance, while knockdown of SNHG12 restored TMZ sensitivity. An abnormally low level of DNA methylation was detected within the promoter region of SNHG12, and loss of DNA methylation made this region more accessible to the Sp1 transcription factor (SP1); this indicated that methylation and SP1 work together to regulate SNHG12 expression. In the cytoplasm, SNHG12 served as a sponge for miR-129-5p, leading to upregulation of MAPK1 and E2F7 and endowing the GBM cells with TMZ resistance. Disinhibition of MAPK1 regulated TMZ-induced cell apoptosis and the G1/S cell cycle transition by activating the MAPK/ERK pathway, while E2F7 dysregulation was primarily associated with G1/S cell cycle transition. Clinically, SNHG12 overexpression was associated with poor survival of GBM patients undergoing TMZ treatment. Conclusion: Our results suggest that SNHG12 could serve as a promising therapeutic target to surmount TMZ resistance, thereby improving the clinical efficacy of TMZ chemotherapy.

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“…Functions of lncRNAs are associated with their subcellular fates. Web servers can assist in quickly assessing experimentally determined or predictive RNA-RNA interactions [204] or even RNA-protein interactions [205,206]. Depending on the subcellular or extracellular compartmental localization of a lncRNA, this patterning will elude to the regulatory role of the gene, as well as how a lncRNA might execute its function [207][208][209].…”

Section: Subcellular Localization and Binding Partnersmentioning

confidence: 99%

The how and why of lncRNA function: An innate immune perspective

Robinson

Covarrubias

2020

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

226

192

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Global Positioning System: Understanding Long Noncoding RNAs through Subcellular Localization

Cited by 234 publications

References 178 publications

Retracted: Long non‐coding RNA ARAP1‐AS1 promotes tumorigenesis and metastasis through facilitating proto‐oncogene c‐Myc translation via dissociating PSF/PTB dimer in cervical cancer

Retracted: Long non‐coding RNA ARAP1‐AS1 promotes tumorigenesis and metastasis through facilitating proto‐oncogene c‐Myc translation via dissociating PSF/PTB dimer in cervical cancer

DNA-methylation-mediated activating of lncRNA SNHG12 promotes temozolomide resistance in glioblastoma

The how and why of lncRNA function: An innate immune perspective

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