The PVT-1 oncogene is a Myc protein target that is overexpressed in transformed cells. (2019) 120:18278–87. Cancer cell. European journal of gastroenterology & hepatology. Silencing of lncRNA expression via administration of specific siRNA oligonucleotides targeting the oncogenic lncRNA CRNDE[48], HOTAIR[39, 111], CCAT2[46], Pvt1 oncogene (PVT1)[58], and uc.73A[59] sequences have been confirmed to exhibit significant anticancer effects, such as decreasing invasion or proliferation either in vivo or in vitro. var thismailbody1 = ""; Poliseno L, Salmena L, Zhang J, Carver B, Haveman WJ, Pandolfi PP. A recent study by Feng et al. Emerging evidence showed that long non-coding RNAs (lncRNAs) play important roles in a wide range of biological processes and dysregulated lncRNAs are involved in many complex human diseases, including cancer. Paraskevopoulou MD, Georgakilas G, Kostoulas N, Reczko M, Maragkakis M, Dalamagas TM. Li Y, Zhuang W, Huang M, Li X. Nucleic acids research. Several lines of evidence indicates that these transcripts contribute in the pathophysiology of HCC (10). PloS one. Du J, Chen M, Liu J, Hu P, Guan H, Jiao X. Lncrna f11-as1 suppresses liver hepatocellular carcinoma progression by competitively binding with mir-3146 to regulate pten expression. Long noncoding RNA SNHG1 predicts a poor prognosis and promotes hepatocellular carcinoma tumorigenesis. De Craene B, Berx G. Regulatory networks defining EMT during cancer initiation and progression. (2020) 19:3054–65. var thismailbody4 = ""; Meulmeester E, Ten Dijke P. The dynamic roles of TGF-beta in cancer. Zhao Z-B, Chen F, Bai X-F. Long Noncoding RNA MALAT1 regulates hepatocellular carcinoma growth under hypoxia via sponging MicroRNA-200a. Long noncoding RNAs : a new player in the prevention and treatment of diabetic cardiomyopathy? doi: 10.1186/s12943-018-0838-5, 25. doi: 10.3389/fphys.2018.01201, 19. Yang X, Yao B, Niu Y, Chen T, Mo H, Wang L, et al. doi: 10.1038/nrendo.2015.216, 14. In another study, Zhao et al. J Exp Clin Cancer Res (2015) 34(1):1–10. lncRNA HOXB-AS3 promotes hepatoma by inhibiting p53 expression. Coincidentally, Nakano et al. In recent years, relevant studies have revealed that long non-coding RNA (lncRNA) is associated with the prognosis of Glioma. J Cell Biochem (2018) 119(6):4458–68. Med Sci Monitor: Int Med J Exp Clin Res (2019) 25:2079. doi: 10.12659/MSM.915541, 106. 2014;42:D98-103 12. Eur Rev Med Pharmacol Sci. Cell Death Dis (2017) 8(10):e3124–e. doi: 10.1007/s13577-019-00269-x, 153. doi: 10.1016/j.bbrc.2019.09.091, 112. In the early phase of tumorigenesis, TGF-β signaling acts as a cancer suppressor. A second lncRNA functioning as a positive moderator of EMT progression in CRC is H19. Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Over-expression of LINC01138 in HCC confers malignant characteristics and is associated with poor survival of patients. Theranostics (2018) 8(10):2814. doi: 10.7150/thno.23012, 152. The pathogenetic mechanisms underlying CRC development are complex. DNA Cell Biol (2018) 37(5):481–90. Downregulating of Kcnq1ot1 can obviously improve these changes. Eur Rev Med Pharmacol Sci (2017) 21(21):4867–74. doi: 10.1038/cddis.2017.321, 8. Long non-coding RNA MNX1-AS1 promotes hepatocellular carcinoma proliferation and invasion through targeting miR-218-5p/COMMD8 axis. Younger ST, Rinn JL. CRNDE, a long non-coding RNA responsive to insulin/IGF signaling, regulates genes involved in central metabolism. Besides, this process is often accompanied by excessive activation of the renin-angiotensin-aldosterone system, which further accelerates cardiac remodeling, including cardiomyocyte hypertrophy, interstitial fibrosis, vascular endothelial cells and vascular smooth muscle cell dysfunction (11). Molecular mechanisms of diabetic cardiomyopathy. doi: 10.1016/j.cell.2018.01.011, 310. Arends JW. doi: 10.1016/j.ejso.2017.06.013, 28. doi: 10.1186/s13046-019-1213-0, 11. Huang Y, Xiang B, Liu Y, Wang Y, Kan H. LncRNA CDKN2B-AS1 promotes tumor growth and metastasis of human hepatocellular carcinoma by targeting let-7c-5p/NAP1L1 axis. Non-coding RNAs participate in the regulatory network of CLDN4 via ceRNA mediated miRNA evasion. A functional variant at a prostate cancer predisposition locus at 8q24 is associated with PVT1 expression. Long intergenic nonprotein coding RNA 0152 promotes hepatocellular carcinoma progression by regulating phosphatidylinositol 3-Kinase/Akt/Mammalian target of rapamycin signaling pathway through miR-139/PIK3CA. Zhai H, Fesler A, Schee K, Fodstad O, Flatmark K, Ju J. HCC-associated lncRNAs can affect gene expression via recruiting epigenetic factors (305), regulation of transcription factors (306), modulation of protein degradation (307) and alteration of phosphorylation of proteins (308). Liver cancer is among the most lethal malignancies among both sexes. doi: 10.3892/mmr.2015.4716, 261. (2017) 43:2062–73. Long non-coding RNA HOTAIR is a powerful predictor of metastasis and poor prognosis and is associated with epithelial-mesenchymal transition in colon cancer. Zhao Y, Kong C-Q, Ye J-Z, Bai T, Luo T, Wang D, et al. Inactivation of the oncosuppressive gene APC is the main rate-limiting step of Wnt signaling, occurring in more than 80% of sporadic CRCs[78, 81]. For instance, the paternally-imprinted, oncofetal lncRNA H19 has been found to be a promising target for CRC therapy[121]. Keywords: long non-coding RNA RMRP, cancer, expression, biomarkers, cell lines Introduction Although protein-coding genes comprise a minor portion of the mammalian genome, it has been revealed that the vast majority of these genomes is transcribed at some level ( Carninci et al., 2005 ; Birney et al., 2007 ). Eur Rev Med Pharmacol Sci (2018) 22(21):7222–32. Ulitsky I, Shkumatava A, Jan CH, Sive H, Bartel DP. However, the observed association between these variants and HCC should be verified in independent samples from different ethnic groups. doi: 10.1080/15384101.2019.1629772, 113. lncRNAs may interact with DNA, RNA or proteins, as tumor suppressor genes or . Fu L, Chen Q, Yao T, Li T, Ying S, Hu Y, et al. 1 and LINC00635 for the diagnosis and prognosis of hepatocellular carcinoma. Loven J, Hoke HA, Lin CY, Lau A, Orlando DA, Vakoc CR. The MYC region upstream contains an large tumor-type-specific super enhancer[86]. Like EGFR, insulin-like growth factor-I receptor (IGF-IR) is also a ubiquitous transmembrane tyrosine kinase that plays crucial roles in colorectal tumorigenesis and progression[89]. review aims to briefly discuss the latest findings regarding the roles and mechanisms of some important lncRNAs in the pathogenesis of certain malignant cancers, including lung, breast, liver, and colorectal cancers, as well as hematological malignancies and neuroblastoma. doi: 10.1038/s41598-019-51872-9, 31. et al. The author further proved HOTAIR exerts protective effects in DCM via functioning as a ceRNA to increase SIRT1 expression by sponging miR-34a (53). Oncotarget (2017) 8(21):34429. doi: 10.18632/oncotarget.16260, 130. Dysregulation of lncRNAs, which serve as either oncogenes or tu The aim of this book is to provide an overview of the importance of exosomes in the biomedical field, which involves in novel implications of exosomes in diagnosis and treatment of cancer and infectious diseases. No use, distribution or reproduction is permitted which does not comply with these terms. Mo M, Liu S, Ma X, Tan C, Wei L, Sheng Y, et al. Oncogene (2018) 37(1):75–85. RNA component of mitochondrial RNA processing endoribonuclease (RMRP) is a non-coding transcript firstly acknowledged for its association with the cartilage-hair hypoplasia (CHH) syndrome, a rare autosomal recessive condition. Wang H, Liang L, Dong Q, Huan L, He J, Li B, et al. However, effective means for diagnosing and treating cervical cancer have yet to be identified. Down-regulation expression of TGFB2-AS1 inhibits the proliferation, migration, invasion and induces apoptosis in HepG2 cells. Eur Rev Med Pharmacol Sci (2019) 23(3):1038–46. Oncofetal H19 is elevated during embryogenesis, but is inactivated postnatally and re-expressed during tumorigenesis[83]. O’Brien A, Zhou T, Tan C, Alpini G, Glaser S. Role of Non-Coding RNAs in the Progression of Liver Cancer: Evidence from Experimental Models. Biosci Rep. (2019) 39:1–7. Gao J, Yin X, Yu X, Dai C, Zhou F. Long noncoding RNA LINC00488 functions as a ceRNA to regulate hepatocellular carcinoma cell growth and angiogenesis through miR-330-5. Long noncoding RNA NKILA enhances the anti-cancer effects of baicalein in hepatocellular carcinoma via the regulation of NF-κB signaling. In vitro, Kcnq1ot1 expression is increased in high glucose-treated cardiac fibroblasts, while the left ventricular contraction and diastolic function is deteriorated. 15 Cancer Med (2019) 8(14):6358–69. doi: 10.1016/j.canlet.2013.01.033, 37. CAHM, a long non-coding RNA gene hypermethylated in colorectal neoplasia. 2010;142:409-19, 104. J Hematol Oncol (2017) 10(1):91. doi: 10.1186/s13045-017-0449-4, 224. Delivery of Loc285194 by plasmid expression vector into CRC cells in xenograft models or in the p53 wild-type CRC cell line HCT-116 significantly suppresses tumor cell growth[65] Although the nucleic acid-based approach for CRC treatment is in the development phase, the lncRNA-based therapeutics for CRC still has several difficulties to overcome. 2014;6:181-91, 100. Following the finding from GWAS, recent transcriptomic analyses revealed that lncRNA expression profiles differed considerably between diabetic cardiomyopathy and other forms of cardiomyopathy (30) LncRNAs have the ability to take part in the development and progression of DCM through multiple pathways, such as gene polymorphism, upregulation or downregulation, methylation, and acetylation. Zhang H, Xing Z, Mani SKK, Bancel B, Durantel D, Zoulim F, et al. J Trans Med (2019) 17(1):1–15. The long noncoding RNA cardiac hypertrophy-related factor plays oncogenic roles in hepatocellular carcinoma by downregulating microRNA-211. Yao W-F, Liu J-W, Huang D-S. MiR-200a inhibits cell proliferation and EMT by down-regulating the ASPH expression levels and affecting ERK and PI3K/Akt pathways in human hepatoma cells. However, the vast majority of lncRNAs have not been tested as potential therapeutic targets, particularly in the context of currently used cancer treatments. Via sequestering miR-200a, MALAT1 increases aspartate-β-hydroxylase (ASPH) levels, thus elevating expression of proteins which are involved in EMT or cell proliferation (20). Cell Physiol Biochem (2016) 38(2):836–46. Huang D, Wei Y, Zhu J, Wang F. Long non-coding RNA SNHG1 functions as a competitive endogenous RNA to regulate PDCD4 expression by sponging miR-195-5p in hepatocellular carcinoma. Biomarkers in precision therapy in colorectal cancer. The authors have declared that no competing interest exists. Zhang J, Cai M, Jiang D, Xu L. Upregulated LncRNA-CCAT1 promotes hepatocellular carcinoma progression by functioning as miR-30c-2-3p sponge. Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, et al. Nature (2009) 458(7235):223–7. 2011;147:1537-50, 20. Received: 03 January 2021; Accepted: 22 March 2021;Published: 21 April 2021. Moreover, upregulation of PCAT1 implied a poorer OS time in patients with CRC[57]. The incidence and mortality rate of cancer has been quickly increasing in the past decades. (2020) 12:718–30. J Cell Physiol (2019) 234(7):10615–24. Yonsei Med J (2018) 59(7):816–26. J Cell Physiol. DNA Cell Biol (2019) 38(8):857–64. Bao J, Chen X, Hou Y, Kang G, Li Q, Xu Y. LncRNA DBH-AS1 facilitates the tumorigenesis of hepatocellular carcinoma by targeting miR-138 via FAK/Src/ERK pathway. Pancreatic cancers, particularly pancreatic ductal adenocarcinoma (PDAC), are very aggressive and have a high mortality rate due to the lack of specific therapies and understanding their pathogenesis. For example, lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) serves as a ceRNA to sponge miR-141 and thus regulates cell growth, proliferation and differentiation in cardiomyocytes (24, 25); (3) acting as host genes to promote the production of miRNAs. For example, Qi and Zhong found that HOTAIR is specifically downregulated in myocardial tissues and serum of DCM patients compared with diabetic patients without cardiomyopathy or healthy controls. qRT-PCR was applied to detect . (2014) 115:668–77. Hepatocellular carcinoma (HCC) is among the utmost deadly human malignancies. RNA helicase DEAD box protein 5 regulates Polycomb repressive complex 2/Hox transcript antisense intergenic RNA function in hepatitis B virus infection and hepatocarcinogenesis. 2015, 45. Gastroenterology report. J Cell Physiol (2019) 234(5):6548–60. Long non-coding RNA HNF1A-AS1 functioned as an oncogene and autophagy promoter in hepatocellular carcinoma through sponging hsa-miR-30b-5p. (2013) 425:3731–46. Moreover, a number of lncRNAs such as HULC confer resistance to chemotherapeutic agents (13), indicating the potential of targeted therapies against these transcripts in enhancement of response of HCC patients to conventional therapeutic options. [70] showed that the bona fide tumor suppressor gene PTENP1, which contains a relatively shorter 3'UTR than that of PTEN, functions as a decoy to bind to the PTEN-targeting miRNAs, allowing for the expression of the PTEN protein. Am J Cardiol. 2008;9:402-12, 105. The incidence and mortality rate of cancer has been quickly increasing in the past decades. The long noncoding RNA AK002107 negatively modulates miR-140-5p and targets TGFBR1 to induce epithelial–mesenchymal transition in hepatocellular carcinoma. Med Sci Monitor: Int Med J Exp Clin Res (2018) 24:8510. doi: 10.12659/MSM.911179. J Exp Clin Cancer Res (2018) 37(1):1–13. Over expression of long non-coding RNA PANDA promotes hepatocellular carcinoma by inhibiting senescence associated inflammatory factor IL8. Besides, uc.134 suppresses the CUL4A-associted ubiquitination of LATS1 and enhances YAPS127 phosphorylation which results in down-regulation of YAP target genes of YAP (223). doi: 10.26355/eurrev_201810_16044, 79. Since then, more and more evidences have suggested that aberrant MIAT is involved in massive diseases, such as diabetic retinopathy, microvascular dysfunction, myocardial infarction and coronary atherosclerotic heart diseases (31, 46). Cancer Sci (2020) 111(5):1582. doi: 10.1111/cas.14372, 24. Other lncRNAs can modulate EMT through sponging a number of miRNAs. var thismailbody11 = ""; LINC00152 promotes cell cycle progression in hepatocellular carcinoma via miR-193a/b-3p/CCND1 axis. However, after the overexpression of H19, autophagy reaction is reduced, and the left ventricular function is remarkably improved. Development of targeted therapy for ovarian cancer mediated by a plasmid expressing diphtheria toxin under the control of H19 regulatory sequences. Dong J, Teng F, Guo W, Yang J, Ding G, Fu Z. lncRNA SNHG8 promotes the tumorigenesis and metastasis by sponging miR-149-5p and predicts tumor recurrence in hepatocellular carcinoma. TSLNC8 is also down-regulated in HCC samples. [39] found that the upregulation of HOTAIR was frequent in stage IV CRC tissues with liver metastases. doi: 10.1038/nrg.2015.10, 23. Meanwhile, the fact that abnormal lncRNA expression in CRC correlates with patient survival or treatment outcome provides the theoretical rationale for utilizing lncRNAs to be promising therapeutical targets. Several lncRNAs have been reported to play a role in the development of hepatocellular carcinoma (HCC). Gene (2018) 679:138–49. Gu J-X, Zhang X, Miao R-C, Xiang X-H, Fu Y-N, Zhang J-Y, et al. NRED: a database of long noncoding RNA expression. The researchers first described the use of a CCAT1-specific peptide nucleic acid (PNA)-based molecular beacons (TO-PNA-MB) to be a powerfulpredictor for specific identification of CRC in vitro, ex vivo, and in vivo[38]. doi: 10.1016/j.biopha.2016.02.036, 57. The cirrhosis-induced carcinogenic alterations have been detected in 90% of HCC patients (3). Molecular carcinogenesis. Bo C, Li X, He L, Zhang S, Li N, An Y. Peng W, Fan H. Long non-coding RNA PANDAR correlates with poor prognosis and promotes tumorigenesis in hepatocellular carcinoma. Jin F, Wang N, Zhu Y, You L, Wang L, De W, et al. Biochem Biophys Res Commun (2019) 516(2):526–32. (55) found that overexpression of Crnde mitigates cardiac fibrosis and enhances cardiac function in the DCM mouse model, while knockdown of Crnde increases collagen deposition in cardiac fibroblasts. Long non-coding RNAs (lncRNAs) can affect expression of genes via diverse mechanisms including recruitment of regulatory protein complexes, acting as a decoy, changing genome organization and modulating the distribution of posttranslational modifications (7).
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