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Journal ArticleDOI

LncRNA CASC2 Interacts With miR-181a to Modulate Glioma Growth and Resistance to TMZ Through PTEN Pathway.

01 Jul 2017-Journal of Cellular Biochemistry (J Cell Biochem)-Vol. 118, Iss: 7, pp 1889-1899
TL;DR: Observations suggest CASC2 up‐regulates PTEN through direct inhibiting miR‐181a and plays an important role in glioma sensitivity to TMZ and may serve as a potential target for cancer diagnosis and treatment.
Abstract: Temozolomide (TMZ)-based chemotherapy is a standard strategy for glioma, while chemoresistance remains a major therapeutic challenge. Recent evidence highlights the crucial regulatory roles of long non-coding RNAs (lncRNA) in tumor biology. However, the roles and regulatory mechanisms of lncRNA cancer susceptibility candidate 2 (CASC2), in glioma tumorigenesis and chemoresistance are poorly understood. In this study, CASC2 expression was down-regulated in glioma tissues and cell lines, and was related to a clinicopathologic features and shorter survival time. Exogenous CACS2 alone was sufficient to inhibit glioma cells' proliferation and amplified TMZ-induced repression of cell proliferation, while CACS2 knockdown could reverse this process. CACS2 overexpression could sensitize TMZ-resistant glioma cells to TMZ, while CACS2 knockdown exerted the opposite function. Moreover, CASC2 could inhibit the miR-181a expression by direct targeting in TMZ-resistant glioma cells. CASC2 up-regulated PTEN protein and down-regulated p-AKT protein through regulating miR-181a, and the effect of CASC2 on PTEN and p-AKT could be partially restored by miR-181a. With TMZ-resistant glioma tissues, miR-181a was up-regulated while PTEN was down-regulated. Taken together, these observations suggest CASC2 up-regulates PTEN through direct inhibiting miR-181a and plays an important role in glioma sensitivity to TMZ and may serve as a potential target for cancer diagnosis and treatment. J. Cell. Biochem. 118: 1889-1899, 2017. © 2017 Wiley Periodicals, Inc.
Citations
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Journal ArticleDOI
TL;DR: This review summarizes the latest insights into the lncRNA field and their functional roles in glioma, therefore evaluating the potential clinical applications of lncRNAs as prospective novel biomarkers and therapeutic targets.
Abstract: Glioma is one of the most prevalent types of primary intracranial carcinoma with varying malignancy grades I–IV and histological subtypes, including astrocytomas, glioblastoma multiform (GBM), oligodendrogliomas and mixed tumors. Glioma is characterized by rapid cell proliferation and angiogenesis, and the WHO grade IV glioblastoma, which is highly malignant with poor prognosis because GBM stem-like cells (GSCs) are resistant to conventional therapy and easily recrudescent, accounts for the majority of gliomas. Consequently, investigations exploring the accurate molecular mechanisms and reliable therapeutic targets for gliomas have drawn extensive attention. Based on the increasing amount of functional lncRNAs aberrantly expressed in glioma tissues and cell lines, lncRNAs might be critical for glioma initiation, progression and other malignant phenotypes. This review summarizes the latest insights into the lncRNA field and their functional roles in glioma, therefore evaluating the potential clinical applications of lncRNAs as prospective novel biomarkers and therapeutic targets.

256 citations

Journal ArticleDOI
TL;DR: Results showed that upregulated lncARSR promotes doxorubicin resistance in HCC via modulating PTEN‐PI3K/Akt pathway, and implied that lnc ARSR may serve as a promising prognostic biomarker and therapeutic target for HCC chemo‐resistance.
Abstract: Hepatocellular carcinoma (HCC) is generally resistant to chemotherapy due to intrinsic or acquired drug resistances. Many molecules and signaling pathways are involved in chemo-resistance of HCC cells. However, the contribution of long noncoding RNA (lncRNA) to chemo-resistance of HCC cells is still largely unknown. In this study, we revealed the critical roles of long noncoding RNA lncARSR in chemo-resistance of HCC cells. lncARSR is upregulated in HCC, associated with large tumor size and advanced BCLC stage, and indicts poor prognosis. Functional assays showed that overexpression of lncARSR enhances doxorubicin resistance of HCC cells in vitro and in vivo. And while knockdown of lncARSR increases sensitivity of HCC cells to doxorubicin in vitro and in vivo. Mechanistically, we found that lncARSR physically associates with PTEN mRNA, promotes PTEN mRNA degradation, decreases PTEN expression, and activates PI3K/Akt pathway. PTEN is downregulated in HCC, and the expression of PTEN is negatively correlated with lncARSR in HCC tissues. Furthermore, the effects of lncARSR overexpression on doxorubicin resistance could be reversed by PI3K/Akt pathway inhibitor, and lncARSR knockdown-induced doxorubicin sensitivity could be reversed by PTEN depletion. Taken together, our results showed that upregulated lncARSR promotes doxorubicin resistance in HCC via modulating PTEN-PI3K/Akt pathway, and implied that lncARSR may serve as a promising prognostic biomarker and therapeutic target for HCC chemo-resistance. J. Cell. Biochem. 118: 4498-4507, 2017. © 2017 Wiley Periodicals, Inc.

95 citations


Cites background from "LncRNA CASC2 Interacts With miR-181..."

  • ...5B), supporting the negative regulation of PTEN by lncARSR. lncARSR ACTIVATES PI3K/Akt PATHWAY PTEN is known to negatively regulate PI3K/Akt pathway and further inhibit tumor progression [Liao et al., 2017; Miao et al., 2017]....

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  • ...lncARSR ACTIVATES PI3K/Akt PATHWAY PTEN is known to negatively regulate PI3K/Akt pathway and further inhibit tumor progression [Liao et al., 2017; Miao et al., 2017]....

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Journal ArticleDOI
22 Dec 2018-Cancers
TL;DR: This paper reviews data of long non-coding RNA expression, which was evaluated in human glioma tissue samples during a five-year period, and summarizes the role of non-Coding RNAs in glioblastoma pathogenesis and the potential application ofNon-c coding RNA species inglioma-grading.
Abstract: Glioma is the most aggressive brain tumor of the central nervous system. The ability of glioma cells to migrate, rapidly diffuse and invade normal adjacent tissue, their sustained proliferation, and heterogeneity contribute to an overall survival of approximately 15 months for most patients with high grade glioma. Numerous studies indicate that non-coding RNA species have critical functions across biological processes that regulate glioma initiation and progression. Recently, new data emerged, which shows that the cross-regulation between long non-coding RNAs and small non-coding RNAs contribute to phenotypic diversity of glioblastoma subclasses. In this paper, we review data of long non-coding RNA expression, which was evaluated in human glioma tissue samples during a five-year period. Thus, this review summarizes the following: (I) the role of non-coding RNAs in glioblastoma pathogenesis, (II) the potential application of non-coding RNA species in glioma-grading, (III) crosstalk between lncRNAs and miRNAs (IV) future perspectives of non-coding RNAs as biomarkers for glioma.

93 citations


Cites background from "LncRNA CASC2 Interacts With miR-181..."

  • ...The elevated expression of miR-181a is associated with lncRNA CASC2 and modulates the resistance to TMZ [44]....

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  • ...Their data shows that the expression of CASC2 influenced the TMZ resistance through the CASC2/miR181a/PTEN pathway [44]....

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  • ...CASC2 also induces chemoresistance by down-regulating the miR-181a/PTEN pathway [44]....

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  • ...miR-181a PTEN pathway LGG-30, HGG-27 Proliferation, chemoresistance to TMZ [44]...

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Journal ArticleDOI
TL;DR: The role and molecular mechanisms of lncRNAs are highlighted and correlation of them with some of the cancers are explained and it is explained that aberrant expression of lNCRNAs in malignancies contributes to the dysregulation of proliferation and differentiation process.
Abstract: Long noncoding RNAs (lncRNAs) constitute large portions of the mammalian transcriptome which appeared as a fundamental player, regulating various cellular mechanisms. LncRNAs do not encode proteins, have mRNA-like transcripts and frequently processed similar to the mRNAs. Many investigations have determined that lncRNAs interact with DNA, RNA molecules or proteins and play a significant regulatory function in several biological processes, such as genomic imprinting, epigenetic regulation, cell cycle regulation, apoptosis, and differentiation. LncRNAs can modulate gene expression on three levels: chromatin remodeling, transcription, and post-transcriptional processing. The majority of the identified lncRNAs seem to be transcribed by the RNA polymerase II. Recent evidence has illustrated that dysregulation of lncRNAs can lead to many human diseases, in particular, cancer. The aberrant expression of lncRNAs in malignancies contributes to the dysregulation of proliferation and differentiation process. Consequently, lncRNAs can be useful to the diagnosis, treatment, and prognosis, and have been characterized as potential cancer markers as well. In this review, we highlighted the role and molecular mechanisms of lncRNAs and their correlation with some of the cancers.

89 citations

Book ChapterDOI
TL;DR: Novel methods and strategies are being developed to study lncRNAs function and will provide researchers with the tools and opportunities to develop lncRNA-based therapeutics for cancer.
Abstract: Long noncoding RNAs (lncRNAs) have recently gained considerable attention as key players in biological regulation; however, the mechanisms by which lncRNAs govern various disease processes remain mysterious and are just beginning to be understood. The ease of next-generation sequencing technologies has led to an explosion of genomic information, especially for the lncRNA class of noncoding RNAs. LncRNAs exhibit the characteristics of mRNAs, such as polyadenylation, 5' methyl capping, RNA polymerase II-dependent transcription, and splicing. These transcripts comprise more than 200 nucleotides (nt) and are not translated into proteins. Directed interrogation of annotated lncRNAs from RNA-Seq datasets has revealed dramatic differences in their expression, largely driven by alterations in transcription, the cell cycle, and RNA metabolism. The fact that lncRNAs are expressed cell- and tissue-specifically makes them excellent biomarkers for ongoing biological events. Notably, lncRNAs are differentially expressed in several cancers and show a distinct association with clinical outcomes. Novel methods and strategies are being developed to study lncRNA function and will provide researchers with the tools and opportunities to develop lncRNA-based therapeutics for cancer.

86 citations

References
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Journal ArticleDOI
Sarah Djebali, Carrie A. Davis1, Angelika Merkel, Alexander Dobin1, Timo Lassmann, Ali Mortazavi2, Ali Mortazavi3, Andrea Tanzer, Julien Lagarde, Wei Lin1, Felix Schlesinger1, Chenghai Xue1, Georgi K. Marinov3, Jainab Khatun4, Brian A. Williams3, Chris Zaleski1, Joel Rozowsky5, Marion S. Röder, Felix Kokocinski6, Rehab F. Abdelhamid, Tyler Alioto, Igor Antoshechkin3, Michael T. Baer1, Nadav Bar7, Philippe Batut1, Kimberly Bell1, Ian Bell8, Sudipto K. Chakrabortty1, Xian Chen9, Jacqueline Chrast10, Joao Curado, Thomas Derrien, Jorg Drenkow1, Erica Dumais8, Jacqueline Dumais8, Radha Duttagupta8, Emilie Falconnet11, Meagan Fastuca1, Kata Fejes-Toth1, Pedro G. Ferreira, Sylvain Foissac8, Melissa J. Fullwood12, Hui Gao8, David Gonzalez, Assaf Gordon1, Harsha P. Gunawardena9, Cédric Howald10, Sonali Jha1, Rory Johnson, Philipp Kapranov8, Brandon King3, Colin Kingswood, Oscar Junhong Luo12, Eddie Park2, Kimberly Persaud1, Jonathan B. Preall1, Paolo Ribeca, Brian A. Risk4, Daniel Robyr11, Michael Sammeth, Lorian Schaffer3, Lei-Hoon See1, Atif Shahab12, Jørgen Skancke7, Ana Maria Suzuki, Hazuki Takahashi, Hagen Tilgner13, Diane Trout3, Nathalie Walters10, Huaien Wang1, John A. Wrobel4, Yanbao Yu9, Xiaoan Ruan12, Yoshihide Hayashizaki, Jennifer Harrow6, Mark Gerstein5, Tim Hubbard6, Alexandre Reymond10, Stylianos E. Antonarakis11, Gregory J. Hannon1, Morgan C. Giddings9, Morgan C. Giddings4, Yijun Ruan12, Barbara J. Wold3, Piero Carninci, Roderic Guigó14, Thomas R. Gingeras8, Thomas R. Gingeras1 
06 Sep 2012-Nature
TL;DR: Evidence that three-quarters of the human genome is capable of being transcribed is reported, as well as observations about the range and levels of expression, localization, processing fates, regulatory regions and modifications of almost all currently annotated and thousands of previously unannotated RNAs that prompt a redefinition of the concept of a gene.
Abstract: Eukaryotic cells make many types of primary and processed RNAs that are found either in specific subcellular compartments or throughout the cells. A complete catalogue of these RNAs is not yet available and their characteristic subcellular localizations are also poorly understood. Because RNA represents the direct output of the genetic information encoded by genomes and a significant proportion of a cell's regulatory capabilities are focused on its synthesis, processing, transport, modification and translation, the generation of such a catalogue is crucial for understanding genome function. Here we report evidence that three-quarters of the human genome is capable of being transcribed, as well as observations about the range and levels of expression, localization, processing fates, regulatory regions and modifications of almost all currently annotated and thousands of previously unannotated RNAs. These observations, taken together, prompt a redefinition of the concept of a gene.

4,450 citations

Journal ArticleDOI
20 Feb 2009-Cell
TL;DR: The evolution of long noncoding RNAs and their roles in transcriptional regulation, epigenetic gene regulation, and disease are reviewed.

4,277 citations


"LncRNA CASC2 Interacts With miR-181..." refers background in this paper

  • ...Emerging evidence has regarded lncRNAs as major regulators of normal development and diseases, including cancer [Ponting et al., 2009]....

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Book ChapterDOI
TL;DR: This chapter focuses on the study of miRNA-lncRNA interactions with either in silico or experimentally supported analyses, and proposes methodologies that can be appropriately adapted in order to become the backbone of advanced multistep functional miRNA analyses.
Abstract: Long noncoding RNAs (lncRNAs) are noncoding transcripts usually longer than 200 nts that have recently emerged as one of the largest and significantly diverse RNA families. The biological role and functions of lncRNAs are still mostly uncharacterized. Their target-mimetic, sponge/decoy function on microRNAs was recently uncovered. miRNAs are a class of noncoding RNA species (~22 nts) that play a central role in posttranscriptional regulation of protein coding genes by mRNA cleavage, direct translational repression and/or mRNA destabilization. LncRNAs can act as miRNA sponges, reducing their regulatory effect on mRNAs. This function introduces an extra layer of complexity in the miRNA-target interaction network. This chapter focuses on the study of miRNA-lncRNA interactions with either in silico or experimentally supported analyses. The proposed methodologies can be appropriately adapted in order to become the backbone of advanced multistep functional miRNA analyses.

638 citations

Journal ArticleDOI
TL;DR: It is concluded that lncRNAs can be used as novel biomarkers in prostate, kidney, or bladder cancer and hold promise as future therapeutic targets.

562 citations


"LncRNA CASC2 Interacts With miR-181..." refers background in this paper

  • ...Human genome sequence data indicate that more than 90% of the DNA sequences actively transcribed, but only 2% of it encodes protein, so most of the transcripts are referred to as non-coding RNAs (ncRNAs) [Djebali et al., 2012; Martens-Uzunova et al., 2014]....

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Journal ArticleDOI
TL;DR: The present work provides the first evidence of a UCA1-miR-204-5p-CREB1/BCL2/RAB22A regulatory network in CRC and reveals that U CA1 and CREB1 are potential new oncogenes and prognostic factors for CRC.
Abstract: Recent preliminary studies reported the in vitro tumor-promoting effects of long non-coding RNA urothelial carcinoma associated 1 (UCA1) in colorectal cancer (CRC). However, the in vivo functions and molecular mechanism of UCA1 in CRC remain unclear. Therefore, we investigated the detailed role and mechanism of UCA1 in CRC. We found that UCA1 was up-regulated in CRCs and negatively correlated with survival time in two CRC cohorts. Functional assays revealed the in vitro and in vivo growth-promoting function of UCA1 and revealed that UCA1 can decrease the sensitivity of CRC cells to 5-FU by attenuating apoptosis. Further mechanistic studies revealed that UCA1 could sponge endogenous miR-204-5p and inhibit its activity. We also identified CREB1 as a new target of miR-204-5p. The protein levels of CREB1 were significantly up-regulated in CRCs, negatively associated with survival time and positively correlated with the UCA1 expression. The present work provides the first evidence of a UCA1-miR-204-5p-CREB1/BCL2/RAB22A regulatory network in CRC and reveals that UCA1 and CREB1 are potential new oncogenes and prognostic factors for CRC.

296 citations


"LncRNA CASC2 Interacts With miR-181..." refers background in this paper

  • ...Another lncRNA, UCA1, enhances 5-fluorouracil resistance in colorectal cancer by inhibiting miR204-5p [Bian et al., 2016]....

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