Overexpressed long noncoding RNA CRNDE with distinct alternatively spliced isoforms in multiple cancers

doi:10.1007/s11684-017-0557-0

Front. Med.

2019, Vol. 13

Issue (3) : 330-343 https://doi.org/10.1007/s11684-017-0557-0

RESEARCH ARTICLE

Overexpressed long noncoding RNA CRNDE with distinct alternatively spliced isoforms in multiple cancers

Xuefei Ma¹, Wei Zhang^1,², Rong Zhang³, Jingming Li¹, Shufen Li¹, Yunlin Ma¹, Wen Jin¹(

), Kankan Wang^1,²(

)

¹. State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
². School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China
³. Department of Hematology, Xi’an Gaoxin Hospital, Xi’an 710075, China

Download: PDF(1661 KB) HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks

Abstract

Alternative splicing is a tightly regulated process that contributes to cancer development. CRNDE is a long noncoding RNA with alternative splicing and is implicated in the pathogenesis of several cancers. However, whether deregulated expression of CRNDE is common and which isoforms are mainly involved in cancers remain unclear. In this study, we report that CRNDE is aberrantly expressed in the majority of solid and hematopoietic malignancies. The investigation of CRNDE expression in normal samples revealed that CRNDE was expressed in a tissue- and cell-specific manner. Further comparison of CRNDE expression in 2938 patient samples from 15 solid and hematopoietic tumors showed that CRNDE was significantly overexpressed in 11 malignancies, including 3 reported and 8 unreported, and also implicated that the overexpressed isoforms differed in various cancer types. Furthermore, anti-cancer drugs could efficiently repress CRNDE overexpression in cancer cell lines and primary samples, and even had different impacts on the expression of CRNDE isoforms. Finally, experimental profiles of 12 alternatively spliced isoforms demonstrated that the spliced variant CRNDE-g was the most highly expressed isoform in multiple cancer types. Collectively, our results emphasize the cancer-associated feature of CRNDE and its spliced isoforms, and may provide promising targets for cancer diagnosis and therapy.

Keywords long noncoding RNA CRNDE alternative splicing

Corresponding Author(s): Wen Jin,Kankan Wang

Just Accepted Date: 12 February 2018 Online First Date: 29 May 2018 Issue Date: 05 June 2019

Cite this article:

Xuefei Ma,Wei Zhang,Rong Zhang, et al. Overexpressed long noncoding RNA CRNDE with distinct alternatively spliced isoforms in multiple cancers[J]. Front. Med., 2019, 13(3): 330-343.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-017-0557-0
https://academic.hep.com.cn/fmd/EN/Y2019/V13/I3/330

Tab.1 GEO data sets used to detect CRNDE expression in 15 types of cancers

Fig.1 Alternatively spliced variants derived from the CRNDE locus. The CRNDE genomic locus (on the reverse strand) and its 12 transcript variants are pictured. The blue boxes and black dotted lines represent exons and introns, respectively. The target regions by Illumina HumanHT-12 V4.0 (ILMN_3250268 and ILMN_3240698) and Affymetrix HG-U133 (238021_s_at and 238022_at) probes are shown on top of the schematic diagram. The sequence gap in CRNDE-f is the unknown sequence region.

Fig.2 The tissue-specific expression pattern of CRNDE in various normal human tissues. The expression data of CRNDE in 109 types of normal tissues are from the Body Atlas, Tissues, at http://www.nextbio.com. The unassayed tissues have been omitted. The median expression level of total tissue types is shown with the blue line. # stands for the expression value of 16 700 in testes and * stands for 6020 in the parotid gland. The data are presented as mean±standard deviation.

Fig.3 Cancer-specific expression patterns of CRNDE in solid tumors. Sixteen microarray data sets were analyzed, encompassing nine types of solid tumors with 596 tumor samples and 274 corresponding normal or adjacent noncancerous controls. The signal intensities of CRNDE detected by 238021_s_at probe are presented by scatter plots in CRC (A), glioma (B), ACC (C), pancreatic tumor (D), prostate cancer (E), ovarian cancer (G), cervical cancer (H), and NSCLC (I). The signal intensity of CRNDE in NMSC was detected by ILMN_3250268 probe (F). The detailed information of the examined data sets can be found in Table 1. Paired or unpaired t-test was performed to analyze significant differences (* P<0.05, ** P<0.01).

Fig.4 Highly expressed CRNDE in the majority of hematopoietic cancers. (A) The microarray data (GSE13159) included 5 types of leukemia encompassing 2022 leukemia samples and 74 corresponding normal controls. The signal intensities of CRNDE expression are shown by scatter plots and detected by 238021_s_at (upper panel) and 238022_at (lower panel) probes. The x-axis represents the five types of indicated leukemia. (B) The expression levels of CRNDE in ATL patient samples were compared with normal CD4-positive T cells by 238021_s_at (upper panel) and 238022_at (lower panel) probes. Unpaired t-test was performed to analyze significant differences (* P<0.05, ** P<0.01).

Fig.5 Repression of overexpressed CRNDE by anti-cancer drugs in cancer cell lines and patient samples. (A) The signal intensities of CRNDE expression levels were detected by two Affymetrix HG-U133 probes, 238021_s_at and 238022_at, in HCT116 cells (GSE15395), DU145 cells (GSE15392), and PBMC cells (GSE15389). (B and C) The relative intensities of CRNDE expression were detected by 238021_s_at and 238022_at probes in HCT116 (B) and DU154 (C) before and after R547 treatment, respectively [²³]. (D) CRNDE expression was detected by ILMN_3250268 probe in macrophages and AML-M5 cell line THP1 with PMA treatment (GSE46599) [²⁴]. (E) The signal intensities of CRNDE were detected by 238021_s_at and 238022_at probes in normal bone marrow samples and CML patient samples before and after imatinib therapy, respectively (GSE33075) [²⁵]. Paired or unpaired t-test was performed to analyze significant differences (* P<0.05, ** P<0.01).

Fig.6 Experimental evidence illustrating the detailed expression patterns of 12 alternatively spliced isoforms of CRNDE in eight types of cancer cell lines. (A) The schematic diagram shows the CRNDE transcripts and fragments amplified by isoform-specific primer pairs. The blue and orange arrows represent exons and retained introns, respectively. The amplified fragments are marked with bidirectional red arrows. Unique sequences for discriminating each isoform are listed above the corresponding isoforms. (B) RT-PCR assays were performed to detect each isoform of CRNDE by corresponding specific primers. In addition, the amplified fragments were visualized by electrophoresis on agarose gels. (C–J) The relative expression of 12 CRNDE isoforms were determined by qRT-PCR assays in CRC cell lines HT29 (C) and HCT116 cells (D), glioma cancer cell lines U251 (E) and U87MG cells (F), AML cell lines Kasumi-1 (G), U937 (H) and THP1 cells (I), and CML cell line K562 cells (J). The x-axis represents 12 isoforms of CRNDE by letters. The y-axis shows the mean 2^−Δ^Ct values from three independent experiments, and error bars represent the standard deviation.

1	Z Zhang, S Pal, Y Bi, J Tchou, RV Davuluri. Isoform level expression profiles provide better cancer signatures than gene level expression profiles. Genome Med 2013; 5(4): 33 https://doi.org/10.1186/gm437 pmid: 23594586
2	K Miura, W Fujibuchi, M Unno. Splice isoforms as therapeutic targets for colorectal cancer. Carcinogenesis 2012; 33(12): 2311–2319 https://doi.org/10.1093/carcin/bgs347 pmid: 23118106
3	P Gellert, Y Ponomareva, T Braun, S Uchida. Noncoder: a web interface for exon array-based detection of long non-coding RNAs. Nucleic Acids Res 2013; 41(1): e20 https://doi.org/10.1093/nar/gks877 pmid: 23012263
4	JE Wilusz, H Sunwoo, DL Spector. Long noncoding RNAs: functional surprises from the RNA world. Genes Dev 2009; 23(13): 1494–1504 https://doi.org/10.1101/gad.1800909 pmid: 19571179
5	AE Kornienko, CP Dotter, PM Guenzl, H Gisslinger, B Gisslinger, C Cleary, R Kralovics, FM Pauler, DP Barlow. Long non-coding RNAs display higher natural expression variation than protein-coding genes in healthy humans. Genome Biol 2016; 17(1): 14 https://doi.org/10.1186/s13059-016-0873-8 pmid: 26821746
6	RA Gupta, N Shah, KC Wang, J Kim, HM Horlings, DJ Wong, MC Tsai, T Hung, P Argani, JL Rinn, Y Wang, P Brzoska, B Kong, R Li, RB West, MJ van de Vijver, S Sukumar, HY Chang. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 2010; 464(7291): 1071–1076 https://doi.org/10.1038/nature08975 pmid: 20393566
7	O Wapinski, HY Chang. Long noncoding RNAs and human disease. Trends Cell Biol 2011; 21(6): 354–361 https://doi.org/10.1016/j.tcb.2011.04.001 pmid: 21550244
8	Y Liu, M Zhang, L Liang, J Li, YX Chen. Over-expression of lncRNA DANCR is associated with advanced tumor progression and poor prognosis in patients with colorectal cancer. Int J Clin Exp Pathol 2015; 8(9): 11480–11484 pmid: 26617879
9	YK Ren, Y Xiao, XB Wan, YZ Zhao, J Li, Y Li, GS Han, XB Chen, QY Zou, GC Wang, CM Lu, YC Xu, YC Wang. Association of long non-coding RNA HOTTIP with progression and prognosis in colorectal cancer. Int J Clin Exp Pathol 2015; 8(9): 11458–11463 pmid: 26617875
10	M Díaz-Beyá, S Brunet, J Nomdedéu, M Pratcorona, A Cordeiro, D Gallardo, L Escoda, M Tormo, I Heras, JM Ribera, R Duarte, MP de Llano, J Bargay, A Sampol, M Nomdedeu, RM Risueño, M Hoyos, J Sierra, M Monzo, A Navarro, J Esteve; Cooperative AML group CETLAM. The lincRNA HOTAIRM1, located in the HOXA genomic region, is expressed in acute myeloid leukemia, impacts prognosis in patients in the intermediate-risk cytogenetic category, and is associated with a distinctive microRNA signature. Oncotarget 2015; 6(31): 31613–31627 pmid: 26436590
11	JH Joo, D Ryu, Q Peng, SP Sugrue. Role of Pnn in alternative splicing of a specific subset of lncRNAs of the corneal epithelium. Mol Vis 2014; 20: 1629–1642 pmid: 25489234
12	H Tilgner, DG Knowles, R Johnson, CA Davis, S Chakrabortty, S Djebali, J Curado, M Snyder, TR Gingeras, R Guigó. Deep sequencing of subcellular RNA fractions shows splicing to be predominantly co-transcriptional in the human genome but inefficient for lncRNAs. Genome Res 2012; 22(9): 1616–1625 https://doi.org/10.1101/gr.134445.111 pmid: 22955974
13	S Massone, I Vassallo, M Castelnuovo, G Fiorino, E Gatta, M Robello, R Borghi, M Tabaton, C Russo, G Dieci, R Cancedda, A Pagano. RNA polymerase III drives alternative splicing of the potassium channel-interacting protein contributing to brain complexity and neurodegeneration. J Cell Biol 2011; 193(5): 851–866 https://doi.org/10.1083/jcb.201011053 pmid: 21624954
14	LD Graham, SK Pedersen, GS Brown, T Ho, Z Kassir, AT Moynihan, EK Vizgoft, R Dunne, L Pimlott, GP Young, LC Lapointe, PL Molloy. Colorectal Neoplasia Differentially Expressed (CRNDE), a novel gene with elevated expression in colorectal adenomas and adenocarcinomas. Genes Cancer 2011; 2(8): 829–840 https://doi.org/10.1177/1947601911431081 pmid: 22393467
15	XL Fu, DJ Liu, TT Yan, JY Yang, MW Yang, J Li, YM Huo, W Liu, JF Zhang, J Hong, R Hua, HY Chen, YW Sun. Analysis of long non-coding RNA expression profiles in pancreatic ductal adenocarcinoma. Sci Rep 2016; 6(1): 33535 https://doi.org/10.1038/srep33535 pmid: 27628540
16	X Zhang, S Sun, JK Pu, AC Tsang, D Lee, VO Man, WM Lui, ST Wong, GK Leung. Long non-coding RNA expression profiles predict clinical phenotypes in glioma. Neurobiol Dis 2012; 48(1): 1–8 https://doi.org/10.1016/j.nbd.2012.06.004 pmid: 22709987
17	BC Ellis, PL Molloy, LD Graham. CRNDE: a long non-coding RNA involved in cancer, neurobiology, and development. Front Genet 2012; 3: 270 https://doi.org/10.3389/fgene.2012.00270 pmid: 23226159
18	P Han, JW Li, BM Zhang, JC Lv, YM Li, XY Gu, ZW Yu, YH Jia, XF Bai, L Li, YL Liu, BB Cui. The lncRNA CRNDE promotes colorectal cancer cell proliferation and chemoresistance via miR-181a-5p-mediated regulation of Wnt/β-catenin signaling. Mol Cancer 2017; 16(1): 9 https://doi.org/10.1186/s12943-017-0583-1 pmid: 28086904
19	K Shao, T Shi, Y Yang, X Wang, D Xu, P Zhou. Highly expressed lncRNA CRNDE promotes cell proliferation through Wnt/β-catenin signaling in renal cell carcinoma. Tumour Biol 2016; 37(12): 15997–16004 https://doi.org/10.1007/s13277-016-5440-0 pmid: 27714674
20	J Zheng, XD Li, P Wang, XB Liu, YX Xue, Y Hu, Z Li, ZQ Li, ZH Wang, YH Liu. CRNDE affects the malignant biological characteristics of human glioma stem cells by negatively regulating miR-186. Oncotarget 2015; 6(28): 25339–25355 https://doi.org/10.18632/oncotarget.4509 pmid: 26231038
21	T Liu, X Zhang, YM Yang, LT Du, CX Wang. Increased expression of the long noncoding RNA CRNDE-h indicates a poor prognosis in colorectal cancer, and is positively correlated with IRX5 mRNA expression. Onco Targets Ther 2016; 9: 1437–1448 pmid: 27042112
22	T Liu, X Zhang, S Gao, F Jing, Y Yang, L Du, G Zheng, P Li, C Li, C Wang. Exosomal long noncoding RNA CRNDE-h as a novel serum-based biomarker for diagnosis and prognosis of colorectal cancer. Oncotarget 2016; 7(51): 85551–85563 pmid: 27888803
23	W Berkofsky-Fessler, TQ Nguyen, P Delmar, J Molnos, C Kanwal, W DePinto, J Rosinski, P McLoughlin, S Ritland, M DeMario, K Tobon, JF Reidhaar-Olson, R Rueger, H Hilton. Preclinical biomarkers for a cyclin-dependent kinase inhibitor translate to candidate pharmacodynamic biomarkers in phase I patients. Mol Cancer Ther 2009; 8(9): 2517–2525 https://doi.org/10.1158/1535-7163.MCT-09-0083 pmid: 19755512
24	C Goujon, O Moncorgé, H Bauby, T Doyle, CC Ward, T Schaller, S Hué, WS Barclay, R Schulz, MH Malim. Human MX2 is an interferon-induced post-entry inhibitor of HIV-1 infection. Nature 2013; 502(7472): 559–562 https://doi.org/10.1038/nature12542 pmid: 24048477
25	R Benito, E Lumbreras, M Abáigar, NC Gutiérrez, M Delgado, C Robledo, JL García, AE Rodríguez-Vicente, MC Cañizo, JM Rivas. Imatinib therapy of chronic myeloid leukemia restores the expression levels of key genes for DNA damage and cell-cycle progression. Pharmacogenet Genomics 2012; 22(5): 381–388 pmid: 22388797
26	BC Ellis, LD Graham, PL Molloy. CRNDE, a long non-coding RNA responsive to insulin/IGF signaling, regulates genes involved in central metabolism. Biochim Biophys Acta 2014; 1843(2): 372–386 https://doi.org/10.1016/j.bbamcr.2013.10.016 pmid: 24184209
27	A Khamas, T Ishikawa, K Shimokawa, K Mogushi, S Iida, M Ishiguro, H Mizushima, H Tanaka, H Uetake, K Sugihara. Screening for epigenetically masked genes in colorectal cancer Using 5-Aza-2′-deoxycytidine, microarray and gene expression profile. Cancer Genomics Proteomics 2012; 9(2): 67–75 pmid: 22399497
28	J Sabates-Bellver, LG Van der Flier, M de Palo, E Cattaneo, C Maake, H Rehrauer, E Laczko, MA Kurowski, JM Bujnicki, M Menigatti, J Luz, TV Ranalli, V Gomes, A Pastorelli, R Faggiani, M Anti, J Jiricny, H Clevers, G Marra. Transcriptome profile of human colorectal adenomas. Mol Cancer Res 2007; 5(12): 1263–1275 https://doi.org/10.1158/1541-7786.MCR-07-0267 pmid: 18171984
29	G Valcz, AV Patai, A Kalmár, B Péterfia, I Fűri, B Wichmann, G Műzes, F Sipos, T Krenács, E Mihály, S Spisák, B Molnár, Z Tulassay. Myofibroblast-derived SFRP1 as potential inhibitor of colorectal carcinoma field effect. PLoS One 2014; 9(11): e106143 https://doi.org/10.1371/journal.pone.0106143 pmid: 25405986
30	O Galamb, B Györffy, F Sipos, S Spisák, AM Németh, P Miheller, Z Tulassay, E Dinya, B Molnár. Inflammation, adenoma and cancer: objective classification of colon biopsy specimens with gene expression signature. Dis Markers 2008; 25(1): 1–16 https://doi.org/10.1155/2008/586721 pmid: 18776587
31	L Sun, AM Hui, Q Su, A Vortmeyer, Y Kotliarov, S Pastorino, A Passaniti, J Menon, J Walling, R Bailey, M Rosenblum, T Mikkelsen, HA Fine. Neuronal and glioma-derived stem cell factor induces angiogenesis within the brain. Cancer Cell 2006; 9(4): 287–300 https://doi.org/10.1016/j.ccr.2006.03.003 pmid: 16616334
32	MJ Demeure, KE Coan, CS Grant, RA Komorowski, E Stephan, S Sinari, D Mount, KJ Bussey. PTTG1 overexpression in adrenocortical cancer is associated with poor survival and represents a potential therapeutic target. Surgery 2013; 154(6): 1405–1416, discussion 1416 https://doi.org/10.1016/j.surg.2013.06.058 pmid: 24238056
33	TJ Giordano, R Kuick, T Else, PG Gauger, M Vinco, J Bauersfeld, D Sanders, DG Thomas, G Doherty, G Hammer. Molecular classification and prognostication of adrenocortical tumors by transcriptome profiling. Clin Cancer Res 2009; 15(2): 668–676 https://doi.org/10.1158/1078-0432.CCR-08-1067 pmid: 19147773
34	H Pei, L Li, BL Fridley, GD Jenkins, KR Kalari, W Lingle, G Petersen, Z Lou, L Wang. FKBP51 affects cancer cell response to chemotherapy by negatively regulating Akt. Cancer Cell 2009; 16(3): 259–266 https://doi.org/10.1016/j.ccr.2009.07.016 pmid: 19732725
35	W Du, Z Cao, T Song, Y Li, Y Liang. A feature selection method based on multiple kernel learning with expression profiles of different types. BioData Min 2017; 10(1): 4 https://doi.org/10.1186/s13040-017-0124-x pmid: 28184251
36	L Badea, V Herlea, SO Dima, T Dumitrascu, I Popescu. Combined gene expression analysis of whole-tissue and microdissected pancreatic ductal adenocarcinoma identifies genes specifically overexpressed in tumor epithelia. Hepatogastroenterology 2008; 55(88): 2016–2027 pmid: 19260470
37	MS Arredouani, B Lu, M Bhasin, M Eljanne, W Yue, JM Mosquera, GJ Bubley, V Li, MA Rubin, TA Libermann, MG Sanda. Identification of the transcription factor single-minded homologue 2 as a potential biomarker and immunotherapy target in prostate cancer. Clin Cancer Res 2009; 15(18): 5794–5802 https://doi.org/10.1158/1078-0432.CCR-09-0911 pmid: 19737960
38	MM Mortensen, S Høyer, AS Lynnerup, TF Ørntoft, KD Sørensen, M Borre, L Dyrskjøt. Expression profiling of prostate cancer tissue delineates genes associated with recurrence after prostatectomy. Sci Rep 2015; 5(1): 16018 https://doi.org/10.1038/srep16018 pmid: 26522007
39	NJ Bowen, LD Walker, LV Matyunina, S Logani, KA Totten, BB Benigno, JF McDonald. Gene expression profiling supports the hypothesis that human ovarian surface epithelia are multipotent and capable of serving as ovarian cancer initiating cells. BMC Med Genomics 2009; 2(1): 71 https://doi.org/10.1186/1755-8794-2-71 pmid: 20040092
40	JA den Boon, D Pyeon, SS Wang, M Horswill, M Schiffman, M Sherman, RE Zuna, Z Wang, SM Hewitt, R Pearson, M Schott, L Chung, Q He, P Lambert, J Walker, MA Newton, N Wentzensen, P Ahlquist. Molecular transitions from papillomavirus infection to cervical precancer and cancer: role of stromal estrogen receptor signaling. Proc Natl Acad Sci U S A 2015; 112(25): E3255– E3264 https://doi.org/10.1073/pnas.1509322112 pmid: 26056290
41	L Hu, J Ai, H Long, W Liu, X Wang, Y Zuo, Y Li, Q Wu, Y Deng. Integrative microRNA and gene profiling data analysis reveals novel biomarkers and mechanisms for lung cancer. Oncotarget 2016; 7(8): 8441–8454 pmid: 26870998
42	BA Jee, H Lim, SM Kwon, Y Jo, MC Park, IJ Lee, HG Woo. Molecular classification of basal cell carcinoma of skin by gene expression profiling. Mol Carcinog 2015; 54(12): 1605–1612 https://doi.org/10.1002/mc.22233 pmid: 25328065
43	YL Choi, K Tsukasaki, MC O’Neill, Y Yamada, Y Onimaru, K Matsumoto, J Ohashi, Y Yamashita, S Tsutsumi, R Kaneda, S Takada, H Aburatani, S Kamihira, T Nakamura, M Tomonaga, H Mano. A genomic analysis of adult T-cell leukemia. Oncogene 2007; 26(8): 1245–1255 https://doi.org/10.1038/sj.onc.1209898 pmid: 16909099
44	JE Payton, NR Grieselhuber, LW Chang, M Murakami, GK Geiss, DC Link, R Nagarajan, MA Watson, TJ Ley. High throughput digital quantification of mRNA abundance in primary human acute myeloid leukemia samples. J Clin Invest 2009; 119(6): 1714–1726 https://doi.org/10.1172/JCI38248 pmid: 19451695
45	A Kohlmann, TJ Kipps, LZ Rassenti, JR Downing, SA Shurtleff, KI Mills, AF Gilkes, WK Hofmann, G Basso, MC Dell’orto, R Foà, S Chiaretti, J De Vos, S Rauhut, PR Papenhausen, JM Hernández, E Lumbreras, AE Yeoh, ES Koay, R Li, WM Liu, PM Williams, L Wieczorek, T Haferlach. An international standardization programme towards the application of gene expression profiling in routine leukaemia diagnostics: the Microarray Innovations in Leukemia Study Prephase. Br J Haematol 2008; 142(5): 802–807 https://doi.org/10.1111/j.1365-2141.2008.07261.x pmid: 18573112
46	T Haferlach, A Kohlmann, L Wieczorek, G Basso, GT Kronnie, MC Béné, J De Vos, JM Hernández, WK Hofmann, KI Mills, A Gilkes, S Chiaretti, SA Shurtleff, TJ Kipps, LZ Rassenti, AE Yeoh, PR Papenhausen, WM Liu, PM Williams, R Foà. Clinical utility of microarray-based gene expression profiling in the diagnosis and subclassification of leukemia: report from the International Microarray Innovations in Leukemia Study Group. J Clin Oncol 2010; 28(15): 2529–2537 https://doi.org/10.1200/JCO.2009.23.4732 pmid: 20406941
47	K Filarsky, A Garding, N Becker, C Wolf, M Zucknick, R Claus, D Weichenhan, C Plass, H Döhner, S Stilgenbauer, P Lichter, D Mertens. Krüppel-like factor 4 (KLF4) inactivation in chronic lymphocytic leukemia correlates with promoter DNA-methylation and can be reversed by inhibition of NOTCH signaling. Haematologica 2016; 101(6): e249–e253 https://doi.org/10.3324/haematol.2015.138172 pmid: 27081174
48	XJ Chu, W DePinto, D Bartkovitz, SS So, BT Vu, K Packman, C Lukacs, Q Ding, N Jiang, K Wang, P Goelzer, X Yin, MA Smith, BX Higgins, Y Chen, Q Xiang, J Moliterni, G Kaplan, B Graves, A Lovey, N Fotouhi. Discovery of [4-Amino-2-(1-methanesulfonylpiperidin-4-ylamino)pyrimidin-5-yl](2,3-difluoro-6- methoxyphenyl)methanone (R547), a potent and selective cyclin-dependent kinase inhibitor with significant in vivo antitumor activity. J Med Chem 2006; 49(22): 6549–6560 https://doi.org/10.1021/jm0606138 pmid: 17064073
49	A Myrthue, BL Rademacher, J Pittsenbarger, B Kutyba-Brooks, M Gantner, DZ Qian, TM Beer. The iroquois homeobox gene 5 is regulated by 1,25-dihydroxyvitamin D3 in human prostate cancer and regulates apoptosis and the cell cycle in LNCaP prostate cancer cells. Clin Cancer Res 2008; 14(11): 3562–3570 https://doi.org/10.1158/1078-0432.CCR-07-4649 pmid: 18519790
50	LM Szafron, A Balcerak, EA Grzybowska, B Pienkowska-Grela, A Podgorska, R Zub, M Olbryt, J Pamula-Pilat, KM Lisowska, E Grzybowska, T Rubel, A Dansonka-Mieszkowska, B Konopka, M Kulesza, M Lukasik, J Kupryjanczyk. The putative oncogene, CRNDE, is a negative prognostic factor in ovarian cancer patients. Oncotarget 2015; 6(41): 43897–43910 pmid: 26556866
51	Y Wang, Y Wang, J Li, Y Zhang, H Yin, B Han. CRNDE, a long-noncoding RNA, promotes glioma cell growth and invasion through mTOR signaling. Cancer Lett 2015; 367(2): 122–128 https://doi.org/10.1016/j.canlet.2015.03.027 pmid: 25813405
52	J Zheng, X Liu, P Wang, Y Xue, J Ma, C Qu, Y Liu. CRNDE promotes malignant progression of glioma by attenuating miR-384/PIWIL4/STAT3 axis. Mol Ther 2016; 24(7): 1199–1215 https://doi.org/10.1038/mt.2016.71 pmid: 27058823
53	H Gao, X Song, T Kang, B Yan, L Feng, L Gao, L Ai, X Liu, J Yu, H Li. Long noncoding RNA CRNDE functions as a competing endogenous RNA to promote metastasis and oxaliplatin resistance by sponging miR-136 in colorectal cancer. Onco Targets Ther 2017; 10: 205–216 https://doi.org/10.2147/OTT.S116178 pmid: 28115855
54	AM Khalil, M Guttman, M Huarte, M Garber, A Raj, D Rivea Morales, K Thomas, A Presser, BE Bernstein, A van Oudenaarden, A Regev, ES Lander, JL Rinn. Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci U S A 2009; 106(28): 11667–11672 https://doi.org/10.1073/pnas.0904715106 pmid: 19571010
55	LM Szafron, A Balcerak, EA Grzybowska, B Pienkowska-Grela, A Felisiak-Golabek, A Podgorska, M Kulesza, N Nowak, P Pomorski, J Wysocki, T Rubel, A Dansonka-Mieszkowska, B Konopka, M Lukasik, J Kupryjanczyk. The novel gene CRNDE encodes a nuclear peptide (CRNDEP) which is overexpressed in highly proliferating tissues. PLoS One 2015; 10(5): e0127475 https://doi.org/10.1371/journal.pone.0127475 pmid: 25978564

[1]

FMD-17042-OF-WKK_suppl_1

Download

[1]	Yanfei Wang,Yueyue Liu,Hongyun Nie,Xin Ma,Zhigang Xu. Alternative splicing of inner-ear-expressed genes[J]. Front. Med., 2016, 10(3): 250-257.

Viewed

Full text

Abstract

Cited

Shared

Discussed