CoChat
Sign Up
Cited by 47Mechanisms of cancer metastasisCancer Mechanisms and TherapyColorectal Cancer Treatments and Studies

Up-regulation of REG3A in colorectal cancer cells confers proliferation and correlates with colorectal cancer risk

Open access
Ye, Ying, Xiao, Ling, Wang, Su-Juan, Yue, Wei, Yin, Qiao-Shan, Sun, Meng-Yao, Xia, Wei, Shao, Zhi-Yi +1 more·2016·Oncotarget
DOI 10.18632/oncotarget.6473PMC PMC4826180
Open this paper in CoChat — free accountOpen PDF

Abstract

// Ying Ye 1,* , Ling Xiao 1,* , Su-Juan Wang 1 , Wei Yue 1 , Qiao-Shan Yin 1 , Meng-Yao Sun 1,2 , Wei Xia 3 , Zhi-Yi Shao 1 and Hong Zhang 1,2 1 Central Laboratory, Shanghai Seventh People’s Hospital, Shanghai, PR China 2 Department of Pharmaceutical Botany, School of Pharmacy, Second Military Medical University, Shanghai, PR China 3 Department of Nuclear Medicine, Shanghai Seventh People’s Hospital, Shanghai, PR China * These authors have contributed equally to this work Correspondence to: Hong Zhang, email: // Wei Xia, email: // Keywords : colorectal cancer; REG3A; AKT; ERK1/2 Received : June 14, 2015 Accepted : November 25, 2015 Published : December 04, 2015 Abstract Colorectal cancer (CRC) is one of the most common malignancies in the world. Previous studies have investigated the altered expression of regenerating islet-derived 3 alpha (REG3A) in various cancers. We aimed at exploring the biological function and the underlying molecular mechanism of REG3A in CRC. In this study, REG3A was found elevated in CRC compared with normal tissues. Further, high REG3A expression level was correlated with bigger tumor size, poorer differentiation, higher tumor stage and lower survival rate. Knockdown of REG3A in two CRC cell lines, LOVO and RKO, significantly inhibited cell proliferation, and increased cells population in G1 phase and cell apoptotic rate. We also found that down-regulation of REG3A in CRC cells notably inhibited cell migration and invasion. Gene set enrichment analysis on The Cancer Genome Atlas dataset showed that Kyoto Encyclopedia of Genes and Genomes (KEGG) DNA replication and base excision repair (BER) pathways were correlative with the REG3A expression, which was further confirmed in CRC cells by Western blot. Moreover, we confirmed the interaction of REG3A and fibronectin in CRC cells. We also found that there was a positive correlation between REG3A expression level and the AKT and ERK1/2 phosphorylation status. These collective data indicated that REG3A overexpression promotes CRC tumorigenesis by activating AKT and ERK1/2 pathways. REG3A may serve as a promising therapeutic strategy for CRC.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.18632/oncotarget.6473

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

No references could be resolved yet.

Research works printed but not linked: 31

  1. [1]Jemal A Bray F Center MM Ferlay J Ward E Forman D Global cancer statistics CA 2011 61 69 90 21296855
  2. [2]Center MM Jemal A Smith RA Ward E Worldwide variations in colorectal cancer CA 2009 59 366 378 19897840
  3. [3]Center MM Jemal A Ward E International trends in colorectal cancer incidence rates Cancer Epidemiology Biomarkers & Prevention 2009 18 1688 1694 19505900
  4. [4]Kuiper JG Phipps AI Neuhouser ML Chlebowski RT Thomson CA Irwin ML Lane DS Wactawski-Wende J Hou L Jackson RD Recreational physical activity, body mass index, and survival in women with colorectal cancer Cancer Causes & Control 2012 23 1939 1948 23053793 PMC3499635
  5. [5]Notterman DA Alon U Sierk AJ Levine AJ Transcriptional gene expression profiles of colorectal adenoma, adenocarcinoma, and normal tissue examined by oligonucleotide arrays Cancer research 2001 61 3124 3130 11306497
  6. [6]Alon U Barkai N Notterman DA Gish K Ybarra S Mack D Levine AJ Broad patterns of gene expression revealed by clustering analysis of tumor and normal colon tissues probed by oligonucleotide arrays Proceedings of the National Academy of Sciences 1999 96 6745 6750 PMC21986 10359783
  7. [7]Lasserre C Christa L Simon MT Vernier P Brechot C A novel gene (HIP) activated in human primary liver cancer Cancer research 1992 52 5089 5095 1325291
  8. [8]Dusetti NJ Frigerio JM Fox MF Swallow DM Dagorn JC Iovanna JL Molecular cloning, genomic organization, and chromosomal localization of the human pancreatitis-associated protein (PAP) gene Genomics 1994 19 108 114 8188210
  9. [9]Christa L Carnot F Simon MT Levavasseur F Stinnakre MG Lasserre C Thepot D Clement B Devinoy E Brechot C HIP/PAP is an adhesive protein expressed in hepatocarcinoma, normal Paneth, and pancreatic cells The American journal of physiology 1996 271 G993 1002 8997243
  10. [10]Liu J-L Cui W Li B Lu Y Possible roles of reg family proteins in pancreatic islet cell growth Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets-Immune, Endocrine & Metabolic Disorders) 2008 8 1 10 18393918
  11. [11]Li L Bachem MG Zhou S Sun Z Chen J Siech M Bimmler D Graf R Pancreatitis-associated protein inhibits human pancreatic stellate cell MMP-1 and -2, TIMP-1 and -2 secretion and RECK expression Pancreatology 2009 9 99 110 10.1159/000178880 19077460 · DOI
  12. [12]Lieu HT Batteux F Simon MT Cortes A Nicco C Zavala F Pauloin A Tralhao JG Soubrane O Weill B Brechot C Christa L HIP/PAP accelerates liver regeneration and protects against acetaminophen injury in mice Hepatology (Baltimore, Md) 2005 42 618 626 16116631
  13. [13]Cavard C Terris B Grimber G Christa L Audard V Radenen-Bussiere B Simon MT Renard CA Buendia MA Perret C Overexpression of regenerating islet-derived 1 alpha and 3 alpha genes in human primary liver tumors with beta-catenin mutations Oncogene 2006 25 599 608 16314847
  14. [14]Yuan RH Jeng YM Chen HL Hsieh FJ Yang CY Lee PH Hsu HC Opposite roles of human pancreatitis-associated protein and REG1A expression in hepatocellular carcinoma: association of pancreatitis-associated protein expression with low-stage hepatocellular carcinoma, beta-catenin mutation, and favorable prognosis Clinical cancer research 2005 11 2568 2575 15814635
  15. [15]Choi B Suh Y Kim W Christa L Park J Bae C Downregulation of regenerating islet-derived 3 alpha (REG3A) in primary human gastric adenocarcinomas Experimental and molecular medicine 2007 39 796 18160850
  16. [16]Rechreche H Montalto G Mallo GV Vasseur S Marasa L Soubeyran P Dagorn JC Iovanna JL pap, reg Iα and reg Iβ mRNAs are concomitantly up-regulated during human colorectal carcinogenesis International journal of cancer 1999 81 688 694 10328217
  17. [17]Han S Khuri FR Roman J Fibronectin stimulates non-small cell lung carcinoma cell growth through activation of Akt/mammalian target of rapamycin/S6 kinase and inactivation of LKB1/AMP-activated protein kinase signal pathways Cancer research 2006 66 315 323 16397245
  18. [18]Vivanco I Sawyers CL The phosphatidylinositol 3-kinase-AKT pathway in human cancer Nature Reviews Cancer 2002 2 489 501 12094235
  19. [19]Altomare DA Testa JR Perturbations of the AKT signaling pathway in human cancer Oncogene 2005 24 7455 7464 16288292
  20. [20]Hilger R Scheulen M Strumberg D The Ras-Raf-MEK-ERK pathway in the treatment of cancer Oncology Research and Treatment 2002 25 511 518 12566895
  21. [21]Lai Y Li D Li C Muehleisen B Radek KA Park HJ Jiang Z Li Z Lei H Quan Y Zhang T Wu Y Kotol P Morizane S Hata TR Iwatsuki K The antimicrobial protein REG3A regulates keratinocyte proliferation and differentiation after skin injury Immunity 2012 37 74 84 22727489 PMC3828049
  22. [22]Kadowaki Y Ishihara S Miyaoka Y Rumi MA Sato H Kazumori H Adachi K Takasawa S Okamoto H Chiba T Kinoshita Y Reg protein is overexpressed in gastric cancer cells, where it activates a signal transduction pathway that converges on ERK1/2 to stimulate growth FEBS letters 2002 530 59 64 12387866
  23. [23]Macadam R Sarela A Farmery S Robinson P Markham A Guillou P Death from early colorectal cancer is predicted by the presence of transcripts of the REG gene family British journal of cancer 2000 83 188 10901369 PMC2363494
  24. [24]Zhang Y Lai M Lv B Gu X Wang H Zhu Y Zhu Y Shao L Wang G Overexpression of Reg IV in colorectal adenoma Cancer letters 2003 200 69 76 14550954
  25. [25]Violette S Festor E Pandrea-Vasile I Mitchell V Adida C Dussaulx E Lacorte JM Chambaz J Lacasa M Lesuffleur T Reg IV, a new member of the regenerating gene family, is overexpressed in colorectal carcinomas International journal of cancer 2003 103 185 193 12455032
  26. [26]Luo M-J Lai M-D Identification of differentially expressed genes in normal mucosa, adenoma and adenocarcinoma of colon by SSH World Journal of Gastroenterology 2001 7 726 731 11819864 PMC4695584
  27. [27]Tachibana KeK Gonzalez MA Coleman N Cell-cycle-dependent regulation of DNA replication and its relevance to cancer pathology The Journal of pathology 2005 205 123 129 15643673
  28. [28]Peralta-Leal A Rodríguez MI Oliver FJ Poly (ADP-ribose) polymerase-1 (PARP-1) in carcinogenesis: potential role of PARP inhibitors in cancer treatment Clinical and Translational Oncology 2008 10 318 323 18558578
  29. [29]Labib K Tercero JA Diffley JF Uninterrupted MCM2-7 function required for DNA replication fork progression Science 2000 288 1643 1647 10834843
  30. [30]Amé JC Spenlehauer C de Murcia G The PARP superfamily Bioessays 2004 26 882 893 15273990
  31. [31]Han S Sidell N Roman J Fibronectin stimulates human lung carcinoma cell proliferation by suppressing p21 gene expression via signals involving Erk and Rho kinase Cancer letters 2005 219 71 81 15694666

Cited by

Sorted by citations

Authors
Ye, Y., Xiao, L., Wang, S.-J., Yue, W., Yin, Q.-S., Sun, M.-Y., Xia, W., Shao, Z.-Y., & Zhang, H.
Affiliations
  • Seventh People's Hospital of Shanghai (CN)
  • Central Laboratory, Shanghai Seventh People's Hospital, Shanghai, PR China
  • Second Military Medical University (CN)
Corresponding author
  • Ye, Ying
  • Xiao, Ling
ORCID
Venue
Oncotarget
Publisher
Impact Journals, LLC
Published
2015-12-04
Volume
7
Issue
4
Pages
3921-3933
ISSN
1949-2553 (ISSN-L)
DOI
10.18632/oncotarget.6473
PMC
PMC4826180
OpenAlex
W2259075699
Cited by
47
References
0
Citations by year
2026: 3 · 2025: 4 · 2024: 11 · 2023: 4 · 2022: 2 · 2021: 2 · 2020: 9 · 2019: 4 · 2018: 2 · 2017: 5
FWCI
1.01
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Oncotarget (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Cancer Mechanisms and Therapy
  • Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
Keywords
REG3A, colorectal cancer, cell proliferation, tumor progression, Akt signaling, ERK signaling, DNA replication, base excision repair, fibronectin, cell migration and invasion, apoptosis, prognostic factors, therapeutic target
MeSH terms
Pancreatitis-Associated Proteins, Adenocarcinoma, Adult, Aged, Animals, Antigens, Neoplasm, Cell Cycle, Female, Flow Cytometry, Fluorescent Antibody Technique, Humans, Immunoenzyme Techniques, Male, Mice, Inbred BALB C, Mice, Nude, Middle Aged, Neoplasm Staging, Prognosis, Risk Factors, RNA, Messenger, Tumor Cells, Cultured, Biomarkers, Tumor, Blotting, Western, Colorectal Neoplasms, Survival Rate, Apoptosis, Reverse Transcriptase Polymerase Chain Reaction, Xenograft Model Antitumor Assays, Lectins, C-Type, Cell Proliferation, Mice, Real-Time Polymerase Chain Reaction

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review