RPSAP52 lncRNA is overexpressed in pituitary tumors and promotes cell proliferation by acting as miRNA sponge for HMGA proteins

D'Angelo, Daniela; Mussnich, Paula; Sepe, Romina; Raia, Maddalena; Vecchio, Luigi Del; Cappabianca, Paolo; Pellecchia, Simona; Petrosino, Sara; Saggio, Serena; Solari, Domenico; Fraggetta, Filippo; Fusco, Alfredo

doi:10.1007/s00109-019-01789-7

Cited by 56 publications

(46 citation statements)

References 39 publications

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“…Increasing evidence indicates that lncRNAs have important regulatory roles in tumorigenesis . The present study confirmed the high expression of LINC00520 in glioma tissues and in glioma cells, and LINC00520 promoted the malignant biological behaviors of glioma cells.…”

Section: Discussionsupporting

confidence: 84%

“…40 Increasing evidence indicates that lncRNAs have important regulatory roles in tumorigenesis. 41,42 The present study confirmed the high expression of LINC00520 in glioma tissues and in F I G U R E 5 Long noncoding RNA (LINC)00520 and microRNA (miR)-520f-3p regulated the expression of transcription factor AP-4 (TFAP4). LINC00520 regulated the expression of LIM and SH3 protein 1 (LASP1) by TFAP4.…”

Section: Discussionsupporting

confidence: 81%

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Transcription factor AP‐4 (TFAP4)‐upstream ORF coding 66 aa inhibits the malignant behaviors of glioma cells by suppressing the TFAP4/long noncoding RNA 00520/microRNA‐520f‐3p feedback loop

et al. 2020

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Upstream ORF (uORF) is a translational initiation element located in the 5′UTR of eukaryotic mRNAs. Studies have found that uORFs play an important regulatory role in many diseases. Based on The Cancer Genome Atlas database, the results of our experiments and previous research evidence, we investigated transcription factor AP‐4 (TFAP4) and its uORF, LIM and SH3 protein 1 (LASP1), long noncoding RNA 00520 (LINC00520), and microRNA (miR)‐520f‐3p as candidates involved in glioma malignancy, which is a poorly understood process. Both TFAP4‐66aa‐uORF and miR‐520f‐3p were downregulated, and TFAP4, LASP1, and LINC00520 were highly expressed in glioma tissues and cells. TFAP4‐66aa‐uORF or miR‐520f‐3p overexpression or TFAP4, LASP1, or LINC00520 knockdown inhibited glioma cell proliferation, migration, and invasion, but promoted apoptosis. TFAP4‐66aa‐uORF inhibited the translation of TFAP4 by binding to the TFAP4 mRNA. MicroRNA‐520f‐3p inhibited TFAP4 expression by binding to its 3′UTR. However, LINC00520 could promote the expression of TFAP4 by competitively binding to miR‐520f‐3p. In addition, TFAP4 transcriptionally activated LASP1 and LINC00520 expression by binding to their promoter regions, forming a positive feedback loop of TFAP4/LINC00520/miR‐520f‐3p. Our findings together indicated that TFAP4‐66aa‐uORF inhibited the TFAP4/LINC00520/miR‐520f‐3p feedback loop by directly inhibiting TFAP4 expression, subsequently leading to inhibition of glioma malignancy. This provides a basis for developing new therapeutic approaches for glioma treatment.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionsupporting

confidence: 81%

Transcription factor AP‐4 (TFAP4)‐upstream ORF coding 66 aa inhibits the malignant behaviors of glioma cells by suppressing the TFAP4/long noncoding RNA 00520/microRNA‐520f‐3p feedback loop

et al. 2020

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“…Indeed, several studies have reported that lncRNAs interact with DNA, RNA, and protein to regulate protein function, induce chromatin remodeling and histone modification, acting as a scaffold, and modulate protein stability and DNA methylation [17][18][19]. The deregulation of lncRNAs has been frequently found in many pathophysiological processes, including cancer, underlying their crucial role in human diseases and considering them as potential diagnostic biomarkers for cancer [20,21].…”

Section: Introductionmentioning

confidence: 99%

The Long Non-Coding RNA Prader Willi/Angelman Region RNA5 (PAR5) Is Downregulated in Anaplastic Thyroid Carcinomas Where It Acts as a Tumor Suppressor by Reducing EZH2 Activity

Pellecchia

Sepe

Decaussin‐Petrucci

et al. 2020

Cancers

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Anaplastic thyroid carcinoma (ATC) represents one the most aggressive neoplasias in humans, and, nowadays, limited advances have been made to extend the survival and reduce the mortality of ATC. Thus, the identification of molecular mechanism underlying its progression is needed. Here, we evaluated the long non-coding RNA (lncRNA) expression profile of nine ATC in comparison with five normal thyroid tissues by a lncRNA microarray. By this analysis, we identified 19 upregulated and 28 downregulated lncRNAs with a fold change >1.1 or <−1.1 and p-value < 0.05, in ATC samples. Some of them were subsequently validated by qRT-PCR. Then, we investigated the role of the lncRNA Prader Willi/Angelman region RNA5 (PAR5), drastically and specifically downregulated in ATC. The restoration of PAR5 reduces proliferation and migration rates of ATC-derived cell lines indicating that its downregulation contributes to thyroid cancer progression. Our results suggest that PAR5 exerts its anti-oncogenic role by impairing Enhancer of Zeste Homolog 2 (EZH2) oncogenic activity since we demonstrated that PAR5 interacts with it in thyroid cancer cell lines, reducing EZH2 protein levels and its binding on the E-cadherin promoter, relieving E-cadherin from the negative regulation by EZH2. Consistently, EZH2 is overexpressed in ATC, but not in differentiated thyroid carcinomas. The results reported here define a tumor suppressor role for PAR5 in undifferentiated thyroid neoplasias, further highlighting the pivotal role of lncRNAs in thyroid carcinogenesis.

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“…The lncRNAs play roles in regulating transcription, translation, and protein translocation [21][22][23][24][25]. LncRNAs can regulate translation by interacting with miRNA or act as precursors of miRNA [26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Identification and analysis of long non-coding RNAs that are involved in inflammatory process in response to transmissible gastroenteritis virus infection

Zhao

Wang

et al. 2019

BMC Genomics

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Background: Transmissible gastroenteritis virus (TGEV) infection can cause acute inflammation. Long noncoding RNAs (lncRNAs) play important roles in a number of biological process including inflammation response. However, whether lncRNAs participate in TGEV-induced inflammation in porcine intestinal epithelial cells (IPECs) is largely unknown. Results: In this study, the next-generation sequencing (NGS) technology was used to analyze the profiles of lncRNAs in Mock and TGEV-infected porcine intestinal epithelial cell-jejunum 2 (IPEC-J2) cell line. A total of 106 lncRNAs were differentially expressed. Many differentially expressed lncRNAs act as elements to competitively attach microRNAs (miRNAs) which target to messenger RNA (mRNAs) to mediate expression of genes that related to tolllike receptors (TLRs), NOD-like receptors (NLRs), tumor necrosis factor (TNF), and RIG-I-like receptors (RLRs) pathways. Functional analysis of the binding proteins and the up/down-stream genes of the differentially expressed lncRNAs revealed that lncRNAs were principally related to inflammatory response. Meanwhile, we found that the differentially expressed lncRNA TCONS_00058367 might lead to a reduction of phosphorylation of transcription factor p65 (p-p65) in TGEV-infected IPEC-J2 cells by negatively regulating its antisense gene promyelocytic leukemia (PML). Conclusions:The data showed that differentially expressed lncRNAs might be involved in inflammatory response induced by TGEV through acting as miRNA sponges, regulating their up/down-stream genes, or directly binding proteins.

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RPSAP52 lncRNA is overexpressed in pituitary tumors and promotes cell proliferation by acting as miRNA sponge for HMGA proteins

Cited by 56 publications

References 39 publications

Transcription factor AP‐4 (TFAP4)‐upstream ORF coding 66 aa inhibits the malignant behaviors of glioma cells by suppressing the TFAP4/long noncoding RNA 00520/microRNA‐520f‐3p feedback loop

Transcription factor AP‐4 (TFAP4)‐upstream ORF coding 66 aa inhibits the malignant behaviors of glioma cells by suppressing the TFAP4/long noncoding RNA 00520/microRNA‐520f‐3p feedback loop

The Long Non-Coding RNA Prader Willi/Angelman Region RNA5 (PAR5) Is Downregulated in Anaplastic Thyroid Carcinomas Where It Acts as a Tumor Suppressor by Reducing EZH2 Activity

Identification and analysis of long non-coding RNAs that are involved in inflammatory process in response to transmissible gastroenteritis virus infection

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