Identifying lrrc16b as an oncofetal gene with transforming enhancing capability using a combined bioinformatics and experimental approach

Nature

Identifying lrrc16b as an oncofetal gene with transforming enhancing capability using a combined bioinformatics and experimental approach"


Play all audios:

Loading...

ABSTRACT Oncofetal genes are expressed in embryos or fetuses, are downregulated or undetectable in adult tissues, and then re-expressed in tumors. Known oncofetal genes, such as _AFP_,


_GCB_, _FGF18_, _IMP-1_ and _SOX1_, often have important clinical applications or pivotal biological functions. To find new oncofetal-like genes, we used the public information of expressed


sequence tags to systematically analyze gene expression patterns and identified a novel oncofetal-like gene, _LRRC16B_. It increased the proliferation, anchorage-independent growth and


tumorigenesis of transformed cells in xenografts, possibly through its effects on cyclin B1 protein levels. These findings exemplify the feasibility of using bioinformatics to find new


oncofetal-like genes and suggest that more genes with important functional roles will be uncovered in the candidate gene list. Access through your institution Buy or subscribe This is a


preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 50 print issues and online access $259.00 per


year only $5.18 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during


checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS SIMULTANEOUS


SCREENING OF OVEREXPRESSED GENES IN BREAST CANCER FOR ONCOGENIC DRIVERS AND TUMOR DEPENDENCIES Article Open access 09 June 2024 GENOMIC STUDIES CONTROVERT THE EXISTENCE OF THE CUX1 P75


ISOFORM Article Open access 07 January 2022 WHOLE-GENOME-SCALE IDENTIFICATION OF NOVEL NON-PROTEIN-CODING RNAS CONTROLLING CELL PROLIFERATION AND SURVIVAL THROUGH A FUNCTIONAL FORWARD


GENETICS STRATEGY Article Open access 07 January 2022 REFERENCES * Adachi-Yamada T, Harumoto T, Sakurai K, Ueda R, Saigo K, O'Connor MB _et al_. (2005). Wing-to-leg homeosis by


spineless causes apoptosis regulated by Fish-lips, a novel leucine-rich repeat transmembrane protein. _Mol Cell Biol_ 25: 3140–3150. Article  CAS  PubMed  PubMed Central  Google Scholar  *


Alexander P . (1970). Mechanism of growth and dissemination of antigenic tumors in normal immunological carriers. _Medicina (B Aires)_ 30: 176–183. CAS  Google Scholar  * Aouacheria A,


Navratil V, Barthelaix A, Mouchiroud D, Gautier C . (2006). Bioinformatic screening of human ESTs for differentially expressed genes in normal and tumor tissues. _BMC Genom_ 7: 94. Article 


Google Scholar  * Barker N, Ridgway RA, van Es JH, van de Wetering M, Begthel H, van den Born M _et al_. (2009). Crypt stem cells as the cells-of-origin of intestinal cancer. _Nature_ 457:


608–611. Article  CAS  PubMed  Google Scholar  * Bergstrand CG, Czar B . (1956). Demonstration of a new protein fraction in serum from the human fetus. _Scand J Clin Lab Invest_ 8: 174.


Article  CAS  PubMed  Google Scholar  * Boguski MS, Schuler GD . (1995). Establishing a human transcript map. _Nat Genet_ 10: 369–371. Article  CAS  PubMed  Google Scholar  * Boiani M,


Scholer HR . (2005). Regulatory networks in embryo-derived pluripotent stem cells. _Nat Rev Mol Cell Biol_ 6: 872–884. Article  CAS  PubMed  Google Scholar  * Campagne F, Skrabanek L .


(2006). Mining expressed sequence tags identifies cancer markers of clinical interest. _BMC Bioinform_ 7: 481. Article  Google Scholar  * Chen CM, Kraut N, Groudine M, Weintraub H . (1996).


I-mf, a novel myogenic repressor, interacts with members of the MyoD family. _Cell_ 86: 731–741. Article  CAS  PubMed  Google Scholar  * Cleynen I, Brants JR, Peeters K, Deckers R,


Debiec-Rychter M, Sciot R _et al_. (2007). HMGA2 regulates transcription of the Imp2 gene via an intronic regulatory element in cooperation with nuclear factor-kappaB. _Mol Cancer Res_ 5:


363–372. Article  CAS  PubMed  Google Scholar  * Colantuoni C, Purcell AE, Bouton CM, Pevsner J . (2000). High throughput analysis of gene expression in the human brain. _J Neurosci Res_ 59:


1–10. Article  CAS  PubMed  Google Scholar  * Cowin AJ, Adams DH, Strudwick XL, Chan H, Hooper JA, Sander GR _et al_. (2007). Flightless I deficiency enhances wound repair by increasing


cell migration and proliferation. _J Pathol_ 211: 572–581. Article  CAS  PubMed  Google Scholar  * Dao DY, Yang X, Chen D, Zuscik M, O'Keefe RJ . (2007). Axin1 and Axin2 are regulated


by TGF- and mediate cross-talk between TGF- and Wnt signaling pathways. _Ann N Y Acad Sci_ 1116: 82–99. Article  CAS  PubMed  PubMed Central  Google Scholar  * Ding S, Schultz PG . (2004). A


role for chemistry in stem cell biology. _Nat Biotechnol_ 22: 833–840. Article  CAS  PubMed  Google Scholar  * Eisenmann KM, Harris ES, Kitchen SM, Holman HA, Higgs HN, Alberts AS . (2007).


Dia-interacting protein modulates formin-mediated actin assembly at the cell cortex. _Curr Biol_ 17: 579–591. Article  CAS  PubMed  Google Scholar  * Esteve P, Bovolenta P . (2006).


Secreted inducers in vertebrate eye development: more functions for old morphogens. _Curr Opin Neurobiol_ 16: 13–19. Article  CAS  PubMed  Google Scholar  * Farghaly SA . (1992). Tumor


markers in gynecologic cancer. _Gynecol Obstet Invest_ 34: 65–72. Article  CAS  PubMed  Google Scholar  * Fukada M, Watakabe I, Yuasa-Kawada J, Kawachi H, Kuroiwa A, Matsuda Y _et al_.


(2000). Molecular characterization of CRMP5, a novel member of the collapsin response mediator rotein family. _J Biol Chem_ 275: 37957–37965. Article  CAS  PubMed  Google Scholar  * Gabory


A, Ripoche MA, Yoshimizu T, Dandolo L . (2006). The H19 gene: regulation and function of a non-coding RNA. _Cytogenet Genome Res_ 113: 188–193. Article  CAS  PubMed  Google Scholar  *


Garcia-Barcelo MM, Lau DK, Ngan ES, Leon TY, Liu TT, So MT _et al_. (2007). Evaluation of the thyroid transcription factor-1 gene (TITF1) as a Hirschsprung's disease locus. _Ann Hum


Genet_ 71: 746–754. Article  CAS  PubMed  Google Scholar  * Gilboa E . (1999). How tumors escape immune destruction and what we can do about it. _Cancer Immunol Immunother_ 48: 382–385.


Article  CAS  PubMed  Google Scholar  * Giles RH, van Es JH, Clevers H . (2003). Caught up in a Wnt storm: Wnt signaling in cancer. _Biochim Biophys Acta_ 1653: 1–24. CAS  PubMed  Google


Scholar  * Grozdanov PN, Yovchev MI, Dabeva MD . (2006). The oncofetal protein glypican-3 is a novel marker of hepatic progenitor/oval cells. _Lab Invest_ 86: 1272–1284. Article  CAS  PubMed


  Google Scholar  * Hishinuma M, Ohashi KI, Yamauchi N, Kashima T, Uozaki H, Ota S _et al_. (2006). Hepatocellular oncofetal protein, glypican 3 is a sensitive marker for


alpha-fetoprotein-producing gastric carcinoma. _Histopathology_ 49: 479–486. Article  CAS  PubMed  Google Scholar  * Hossain MS, Ozaki T, Wang H, Nakagawa A, Takenobu H, Ohira M _et al_.


(2008). N-MYC promotes cell proliferation through a direct transactivation of neuronal leucine-rich repeat protein-1 (NLRR1) gene in neuroblastoma. _Oncogene_ 27: 6075–6082. Article  CAS 


PubMed  Google Scholar  * Imamura F, Nagao H, Naritsuka H, Murata Y, Taniguchi H, Mori K . (2006). A leucine-rich repeat membrane protein, 5T4, is expressed by a subtype of granule cells


with dendritic arbors in specific strata of the mouse olfactory bulb. _J Comp Neurol_ 495: 754–768. Article  CAS  PubMed  Google Scholar  * Kato T, Hayama S, Yamabuki T, Ishikawa N, Miyamoto


M, Ito T _et al_. (2007). Increased expression of insulin-like growth factor-II messenger RNA-binding protein 1 is associated with tumor progression in patients with lung cancer. _Clin


Cancer Res_ 13: 434–442. Article  CAS  PubMed  Google Scholar  * Katoh M . (2007). Networking of WNT, FGF, Notch, BMP, and Hedgehog signaling pathways during carcinogenesis. _Stem Cell Rev_


3: 30–38. Article  CAS  PubMed  Google Scholar  * Katoh M, Katoh M . (2007). WNT antagonist, DKK2, is a Notch signaling target in intestinal stem cells: augmentation of a negative regulation


system for canonical WNT signaling pathway by the Notch-DKK2 signaling loop in primates. _Int J Mol Med_ 19: 197–201. CAS  PubMed  Google Scholar  * Kobe B, Kajava AV . (2001). The


leucine-rich repeat as a protein recognition motif. _Curr Opin Struct Biol_ 11: 725–732. Article  CAS  PubMed  Google Scholar  * Kopecki Z, Cowin AJ . (2008). Flightless I: an


actin-remodelling protein and an important negative regulator of wound repair. _Int J Biochem Cell Biol_ 40: 1415–1419. Article  CAS  PubMed  Google Scholar  * Kutay U, Guttinger S . (2005).


Leucine-rich nuclear-export signals: born to be weak. _Trends Cell Biol_ 15: 121–124. Article  CAS  PubMed  Google Scholar  * Liu CI, Cheng TL, Chen SZ, Huang YC, Chang WT . (2005). LrrA, a


novel leucine-rich repeat protein involved in cytoskeleton remodeling, is required for multicellular morphogenesis in _Dictyostelium discoideum_. _Dev Biol_ 285: 238–251. Article  CAS 


PubMed  Google Scholar  * Matouk IJ, DeGroot N, Mezan S, Ayesh S, Abu-lail R, Hochberg A _et al_. (2007). The H19 non-coding RNA is essential for human tumor growth. _PLoS ONE_ 2: e845.


Article  PubMed  PubMed Central  Google Scholar  * McNamee D . (1995). Beta-hCG inhibits Kaposi's sarcoma. _Lancet_ 345: 1169. Article  CAS  PubMed  Google Scholar  * Monk M, Holding C


. (2001). Human embryonic genes re-expressed in cancer cells. _Oncogene_ 20: 8085–8091. Article  CAS  PubMed  Google Scholar  * Morton JP, Mongeau ME, Klimstra DS, Morris JP, Lee YC,


Kawaguchi Y _et al_. (2007). Sonic hedgehog acts at multiple stages during pancreatic tumorigenesis. _Proc Natl Acad Sci USA_ 104: 5103–5108. Article  CAS  PubMed  PubMed Central  Google


Scholar  * Nielsen J, Christiansen J, Lykke-Andersen J, Johnsen AH, Wewer UM, Nielsen FC . (1999). A family of insulin-like growth factor II mRNA-binding proteins represses translation in


late development. _Mol Cell Biol_ 19: 1262–1270. Article  CAS  PubMed  PubMed Central  Google Scholar  * Niemann H, Carnwath JW, Kues W . (2007). Application of DNA array technology to


mammalian embryos. _Theriogenology_ 68 (Suppl 1): S165–S177. Article  CAS  PubMed  Google Scholar  * Park TJ, Kim JY, Park SH, Kim HS, Lim IK . (2009). Skp2 enhances polyubiquitination and


degradation of TIS21/BTG2/PC3, tumor suppressor protein, at the downstream of FoxM1. _Exp Cell Res_ 315: 3152–3162. Article  CAS  PubMed  Google Scholar  * Qiao M, Iglehart JD, Pardee AB .


(2007). Metastatic potential of 21T human breast cancer cells depends on Akt/protein kinase B activation. _Cancer Res_ 67: 5293–5299. Article  CAS  PubMed  Google Scholar  * Sarandakou A,


Protonotariou E, Rizos D . (2007). Tumor markers in biological fluids associated with pregnancy. _Crit Rev Clin Lab Sci_ 44: 151–178. Article  CAS  PubMed  Google Scholar  * Shimokawa T,


Furukawa Y, Sakai M, Li M, Miwa N, Lin YM _et al_ (2003). Involvement of the FGF18 gene in colorectal carcinogenesis, as a novel downstream target of the beta-catenin/T-cell factor complex.


_Cancer Res_ 63: 6116–6120. CAS  PubMed  Google Scholar  * Sugimori M, Nagao M, Parras CM, Nakatani H, Lebel M, Guillemot F _et al_. (2008). Ascl1 is required for oligodendrocyte development


in the spinal cord. _Development_ 135: 1271–1281. Article  CAS  PubMed  Google Scholar  * Trojan J, Naval X, Johnson T, Lafarge-Frayssinet C, Hajeri-Germond M, Farges O _et al_. (1995).


Expression of serum albumin and of alphafetoprotein in murine normal and neoplastic primitive embryonic structures. _Mol Reprod Dev_ 42: 369–378. Article  CAS  PubMed  Google Scholar  *


Vogelstein B, Kinzler KW . (2004). Cancer genes and the pathways they control. _Nat Med_ 10: 789–799. Article  CAS  PubMed  Google Scholar  * Wang R, Kaul A, Sperry AO . (2009). TLRR


(lrrc67) interacts with PP1 and is associated with a cytoskeletal complex in the testis. _Biol Cell_ 102: 173–189. Article  Google Scholar  * Xu L, Geman D, Winslow RL . (2007). Large-scale


integration of cancer microarray data identifies a robust common cancer signature. _BMC Bioinform_ 8: 275. Article  Google Scholar  Download references ACKNOWLEDGEMENTS This was supported by


Grant NSC-95-2320-B-006-057-MY2 from the National Science Council, Taiwan, and Grant DOH99-TD-C-111-003 from the Department of Health, Taiwan. There is no competing financial interest in


relation to this work. AUTHOR INFORMATION Author notes * C-W Chiang, H-C Cheng and W-T Chang: These authors contributed equally to this work. AUTHORS AND AFFILIATIONS * Institute of Basic


Medical Science, College of Medicine, National Cheng Kung University, Tainan, Taiwan C-C Hsu, C-W Chiang, H-C Cheng, W-T Chang, T-Y Lee, N-H Chow & C-L Ho * Institute of Molecular


Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan C-W Chiang, Z-H Wu, N-H Chow & C-L Ho * Department of Obstetrics and Gynecology, National Cheng Kung


University Hospital, Tainan, Taiwan C-Y Chou * Department of Pathology, National Cheng Kung University Hospital, Tainan, Taiwan H-W Tsai, C-T Lee, N-H Chow & C-L Ho * Department of


Ophthalmology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, Taiwan A Chao Authors * C-C Hsu View author publications You can also search for this author


inPubMed Google Scholar * C-W Chiang View author publications You can also search for this author inPubMed Google Scholar * H-C Cheng View author publications You can also search for this


author inPubMed Google Scholar * W-T Chang View author publications You can also search for this author inPubMed Google Scholar * C-Y Chou View author publications You can also search for


this author inPubMed Google Scholar * H-W Tsai View author publications You can also search for this author inPubMed Google Scholar * C-T Lee View author publications You can also search for


this author inPubMed Google Scholar * Z-H Wu View author publications You can also search for this author inPubMed Google Scholar * T-Y Lee View author publications You can also search for


this author inPubMed Google Scholar * A Chao View author publications You can also search for this author inPubMed Google Scholar * N-H Chow View author publications You can also search for


this author inPubMed Google Scholar * C-L Ho View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to C-L Ho. ETHICS


DECLARATIONS COMPETING INTERESTS The authors declare no conflict of interest. ADDITIONAL INFORMATION Supplementary Information accompanies the paper on the Oncogene website SUPPLEMENTARY


INFORMATION SUPPLEMENTARY FIGURE S1 (JPG 792 KB) SUPPLEMENTARY FIGURE S2 (JPG 365 KB) SUPPLEMENTARY FIGURE S3 (JPG 2761 KB) SUPPLEMENTARY FIGURE S4 (JPG 1834 KB) SUPPLEMENTARY FIGURE S5 (DOC


42 KB) SUPPLEMENTARY FIGURE LEGENDS (DOC 34 KB) SUPPLEMENTARY FIGURE 5 LEGEND (DOC 23 KB) SUPPLEMENTARY TABLE S1 (DOC 82 KB) SUPPLEMENTARY TABLE S2 (DOC 51 KB) SUPPLEMENTARY TABLE S3 (DOC


50 KB) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Hsu, CC., Chiang, CW., Cheng, HC. _et al._ Identifying _LRRC16B_ as an oncofetal gene with


transforming enhancing capability using a combined bioinformatics and experimental approach. _Oncogene_ 30, 654–667 (2011). https://doi.org/10.1038/onc.2010.451 Download citation * Received:


07 February 2010 * Revised: 09 August 2010 * Accepted: 24 August 2010 * Published: 22 November 2010 * Issue Date: 10 February 2011 * DOI: https://doi.org/10.1038/onc.2010.451 SHARE THIS


ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard


Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * oncofetal genes * expressed sequence tags * _LRRC16B_


Trending News

Must-know foodie tips on shopping, prepping and staying fit

DEAN ORNISH, M.D., 70, LIFESTYLE MEDICINE SPECIALIST AND BEST-SELLING AUTHOR Ornish will always be known as the man who ...

How Sheila E. Overcame ‘Girls Don't Play Percussion'

1:32 AARP Videos How Sheila E. Overcame ‘Girls Don't Play Percussion' Singer-percussionist Sheila E. was born into a mus...

Disaster relief grant helps vulnerable older adults

When Hurricane Ida slammed into the Louisiana coast in August 2021, it pummeled communities across the state, leaving a ...

What time is mike tyson vs. Jake paul? How to watch tonight’s fight on netflix

Page Six may be compensated and/or receive an affiliate commission if you click or buy through our links. Featured prici...

Forthcoming Events | Nature

ABSTRACT [_Meetings marked with an asterisk are open to the public_] Access through your institution Buy or subscribe Th...

Latests News

Identifying lrrc16b as an oncofetal gene with transforming enhancing capability using a combined bioinformatics and experimental approach

ABSTRACT Oncofetal genes are expressed in embryos or fetuses, are downregulated or undetectable in adult tissues, and th...

Meet pasteur and see how understanding microbes changed lives for the better

PART 2: MICROBES AS CAUSES OF DISEASE, AND THE QUEST FOR VACCINES AN EARLY IMPRESSION OF RABIES’ DANGERS In October 1831...

5 steps to set boundaries while working from home

With most of the country now under stay-at-home orders to deter the spread of the new coronavirus, millions of Americans...

Flashback: bruce springsteen and pete seeger sing 'this land is your land' for obama

We’re just one day away from Joe Biden’s inauguration as America’s 46th president. This year’s ceremony is going to be a...

The assay of the effect of chemical agents on tumour invasion using chick embryos

Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ...

Top