Login to MyKarger

New to MyKarger? Click here to sign up.



Login with Facebook

Forgot your password?

Authors, Editors, Reviewers

For Manuscript Submission, Check or Review Login please go to Submission Websites List.

Submission Websites List

Institutional Login
(Shibboleth or OpenAthens)

For the academic login, please select your country in the dropdown list. You will be redirected to verify your credentials.

Original Paper

Open Access Gateway

The Functional Variant in the 3'UTR of IGF1 with the Risk of Gastric Cancer in a Chinese Population

Jiang H.a, b · Wang H.b · Ge F.b · Wu L.a · Wang X.a · Chen S.a

Author affiliations

aDepartment of Microbiology, Jiangsu University, ZhenJiang, bLaboratory of Medicine, Chinese traditional Hospital of Jiangyin, Wuxi, China

Corresponding Author

Chen Shengxia, PhD,

Department of Microbiology, School of Medicine, Jiangsu University, ZhenJiang, 212000

(China)

E-Mail Chensx313@163.com

Related Articles for ""

Cell Physiol Biochem 2015;36:884-892

Do you have an account?

Login Information





Contact Information











I have read the Karger Terms and Conditions and agree.



Abstract

Background/Aims: IGF-1 can act as an endocrine hormone and its signaling server as essential roles in regulating tumorigenesis. Polymorphisms in IGF-1 have been reported associated bad prognosis of with human cancer, but their association with the risk of human gastric cancer (GC) has not been found so far. In this study rs6218 located in the 3'UTR of IGF-1 was selected to evaluate its relationship with the risk of GC among Chinese population. Methods: Questionnaire, SNaPshot genotype assay, real time PCR assay, cell transfection and the dual luciferase reporter assay were used in our study. Results: SNP rs6218 in IGF-1 3'-UTR was involved in the occurrence of GC by acting as a tumor promotion factor while rs6128 acting as a risk factor. SNP rs6128 was also could be regulated by miR-603 which caused an up-regulation of IGF-1 in patients with UC and CC genotype. Furthermore, the carriers of UC and CC genotype presented a big tumor size as well as the high probability of metastasis. Conclusion: In conclusion, our findings have shown that the SNP rs6218 in IGF-1 3'-UTR, through disrupting the regulatory role of miR-603 in IGF-1 expression, rs16128 in IGF-1 might act as a promotion factor in the pathogenesis of GC.

© 2015 S. Karger AG, Basel


References

  1. McLean MH, El-Omar EM: Genetics of gastric cancer. Nat Rev Gastroenterol Hepatol 2014;10.1038/nrgastro.2014.143.
  2. Sahin IH, Hassan MM, Garrett CR: Impact of non-steroidal anti-inflammatory drugs on gastrointestinal cancers: current state-of-the science. Cancer Lett 2014;345:249-257.
  3. Wang F, Meng W, Wang B, Qiao L: Helicobacter pylori-induced gastric inflammation and gastric cancer. Cancer Lett 2014;345:196-202.
  4. Subramanyam D, Lamouille S, Judson RL, Liu JY, Bucay N, Derynck R, Blelloch R: Multiple targets of miR-302 and miR-372 promote reprogramming of human fibroblasts to induced pluripotent stem cells. Nat Biotechnol 2011;29:443-448.
  5. Qin YR, Tang H, Xie F, Liu H, Zhu Y, Ai J, Chen L, Li Y, Kwong DL, Fu L, Guan XY: Characterization of tumor-suppressive function of SOX6 in human esophageal squamous cell carcinoma. Clin Cancer Res 2011;17:46-55.
  6. Vinci S, Gelmini S, Pratesi N, Conti S, Malentacchi F, Simi L, Pazzagli M, Orlando C: Genetic variants in miR-146a, miR-149, miR-196a2, miR-499 and their influence on relative expression in lung cancers. Clin Chem Lab Med 2011;49:2073-2080.
  7. Wang H, Zhang P, Chen W, Feng D, Jia Y, Xie LX: Evidence for serum miR-15a and miR-16 levels as biomarkers that distinguish sepsis from systemic inflammatory response syndrome in human subjects. Clin Chem Lab Med 2012;50:1423-1428.
  8. Hirajima S, Komatsu S, Ichikawa D, Takeshita H, Konishi H, Shiozaki A, Morimura R, Tsujiura M, Nagata H, Kawaguchi T, Arita T, Kubota T, Fujiwara H, Okamoto K, Otsuji E: Clinical impact of circulating miR-18a in plasma of patients with oesophageal squamous cell carcinoma. Br J Cancer 2013;bjc2013148 [pii]. Doi 10.1038/bjc.2013.148
  9. Wang ZW, Zhang W, Dong W, Li BS, Mu DB, Huang W, Zhang J, Li HS, Zhang ZC, Lin HQ, Yi Y: Pathological analysis of extracapsular extension of metastatic lymph node and its potential impact on nodal clinical target volume in the radiotherapy of esophageal squamous cell carcinoma. Neoplasma 2014;61:324-330.
  10. Tian Z, Yao G, Song H, Zhou Y, Geng J: IGF2R expression is associated with the chemotherapy response and prognosis of patients with advanced NSCLC. Cell Physiol Biochem 2014;34:1578-1588.
  11. Chen J, Zhao X, Ye Y, Wang Y, Tian J: Estrogen receptor beta-mediated proliferative inhibition and apoptosis in human breast cancer by calycosin and formononetin. Cell Physiol Biochem 2013;32:1790-1797.
  12. Brana I, Berger R, Golan T, Haluska P, Edenfield J, Fiorica J, Stephenson J, Martin LP, Westin S, Hanjani P, Jones MB, Almhanna K, Wenham RM, Sullivan DM, Dalton WS, Gunchenko A, Cheng JD, Siu LL, Gray JE: A parallel-arm phase I trial of the humanised anti-IGF-1R antibody dalotuzumab in combination with the AKT inhibitor MK-2206, the mTOR inhibitor ridaforolimus, or the NOTCH inhibitor MK-0752, in patients with advanced solid tumours. Br J Cancer 2014;111:1932-1944.
  13. Gryko M, Kisluk J, Cepowicz D, Zinczuk J, Kamocki Z, Guzinska-Ustymowicz K, Pryczynicz A, Czyzewska J, Kemona A, Kedra B: Expression of insulin-like growth factor receptor type 1 correlate with lymphatic metastases in human gastric cancer. Pol J Pathol 2014;65:135-140.
  14. Li S, Lei X, Zhang J, Yang H, Liu J, Xu C: Insulin-like growth factor 1 promotes growth of gastric cancer by inhibiting foxo1 nuclear retention. Tumour Biol 2015;10.1007/s13277-015-3096-9
  15. Tamura F, Sato Y, Hirakawa M, Yoshida M, Ono M, Osuga T, Okagawa Y, Uemura N, Arihara Y, Murase K, Kawano Y, Iyama S, Takada K, Hayashi T, Sato T, Miyanishi K, Kobune M, Takimoto R, Kato J: RNAi-mediated gene silencing of ST6GalNAc I suppresses the metastatic potential in gastric cancer cells. Gastric Cancer 2014;10.1007/s10120-014-0454-z
  16. Li H, Li Y, Liu D, Sun H, Liu J: miR-224 is critical for celastrol-induced inhibition of migration and invasion of hepatocellular carcinoma cells. Cell Physiol Biochem 2013;32:448-458.
  17. Plasterk RH: Micro RNAs in animal development. Cell 2006;124:877-881.
  18. Valastyan S, Reinhardt F, Benaich N, Calogrias D, Szasz AM, Wang ZC, Brock JE, Richardson AL, Weinberg RA: A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis. Cell 2009;137:1032-1046.
  19. Hyun S, Lee JH, Jin H, Nam J, Namkoong B, Lee G, Chung J, Kim VN: Conserved MicroRNA miR-8/miR-200 and its target USH/FOG2 control growth by regulating PI3K. Cell 2009;139:1096-1108.
  20. Wang K, Diskin SJ, Zhang H, Attiyeh EF, Winter C, Hou C, Schnepp RW, Diamond M, Bosse K, Mayes PA, Glessner J, Kim C, Frackelton E, Garris M, Wang Q, Glaberson W, Chiavacci R, Nguyen L, Jagannathan J, Saeki N, Sasaki H, Grant SF, Iolascon A, Mosse YP, Cole KA, Li H, Devoto M, McGrady PW, London WB, Capasso M, Rahman N, Hakonarson H, Maris JM: Integrative genomics identifies LMO1 as a neuroblastoma oncogene. Nature 2011;469:216-220.
  21. Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004;116:281-297.
  22. Wang Y, Zhou L, Chen J, Li J, He L, Wu P, Wang M, Tong N, Zhang Z, Fang Y: Association of the 3'UTR FOXO3a polymorphism rs4946936 with an increased risk of childhood acute lymphoblastic leukemia in a Chinese population. Cell Physiol Biochem 2014;34:325-332.
  23. Hernandez W, Grenade C, Santos ER, Bonilla C, Ahaghotu C, Kittles RA: IGF-1 and IGFBP-3 gene variants influence on serum levels and prostate cancer risk in African-Americans. Carcinogenesis 2007;28:2154-2159.
  24. Gu MJ, Bae YK, Choi JH: Clinical significance of insulin-growth factor 1 and insulin-growth factor 1 receptor expression in gastrointestinal stromal tumors. Hepatogastroenterology 2013;60:1383-1386.
    External Resources
  25. Li H, Xu L, Zhao L, Ma Y, Zhu Z, Liu Y, Qu X: Insulin-like growth factor-I induces epithelial to mesenchymal transition via GSK-3beta and ZEB2 in the BGC-823 gastric cancer cell line. Oncol Lett 2015;9:143-148.

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Accepted: April 13, 2015
Published online: June 09, 2015
Issue release date: June 2015

Number of Print Pages: 9
Number of Figures: 3
Number of Tables: 4

ISSN: 1015-8987 (Print)
eISSN: 1421-9778 (Online)

For additional information: https://www.karger.com/CPB

References

  1. McLean MH, El-Omar EM: Genetics of gastric cancer. Nat Rev Gastroenterol Hepatol 2014;10.1038/nrgastro.2014.143.
  2. Sahin IH, Hassan MM, Garrett CR: Impact of non-steroidal anti-inflammatory drugs on gastrointestinal cancers: current state-of-the science. Cancer Lett 2014;345:249-257.
  3. Wang F, Meng W, Wang B, Qiao L: Helicobacter pylori-induced gastric inflammation and gastric cancer. Cancer Lett 2014;345:196-202.
  4. Subramanyam D, Lamouille S, Judson RL, Liu JY, Bucay N, Derynck R, Blelloch R: Multiple targets of miR-302 and miR-372 promote reprogramming of human fibroblasts to induced pluripotent stem cells. Nat Biotechnol 2011;29:443-448.
  5. Qin YR, Tang H, Xie F, Liu H, Zhu Y, Ai J, Chen L, Li Y, Kwong DL, Fu L, Guan XY: Characterization of tumor-suppressive function of SOX6 in human esophageal squamous cell carcinoma. Clin Cancer Res 2011;17:46-55.
  6. Vinci S, Gelmini S, Pratesi N, Conti S, Malentacchi F, Simi L, Pazzagli M, Orlando C: Genetic variants in miR-146a, miR-149, miR-196a2, miR-499 and their influence on relative expression in lung cancers. Clin Chem Lab Med 2011;49:2073-2080.
  7. Wang H, Zhang P, Chen W, Feng D, Jia Y, Xie LX: Evidence for serum miR-15a and miR-16 levels as biomarkers that distinguish sepsis from systemic inflammatory response syndrome in human subjects. Clin Chem Lab Med 2012;50:1423-1428.
  8. Hirajima S, Komatsu S, Ichikawa D, Takeshita H, Konishi H, Shiozaki A, Morimura R, Tsujiura M, Nagata H, Kawaguchi T, Arita T, Kubota T, Fujiwara H, Okamoto K, Otsuji E: Clinical impact of circulating miR-18a in plasma of patients with oesophageal squamous cell carcinoma. Br J Cancer 2013;bjc2013148 [pii]. Doi 10.1038/bjc.2013.148
  9. Wang ZW, Zhang W, Dong W, Li BS, Mu DB, Huang W, Zhang J, Li HS, Zhang ZC, Lin HQ, Yi Y: Pathological analysis of extracapsular extension of metastatic lymph node and its potential impact on nodal clinical target volume in the radiotherapy of esophageal squamous cell carcinoma. Neoplasma 2014;61:324-330.
  10. Tian Z, Yao G, Song H, Zhou Y, Geng J: IGF2R expression is associated with the chemotherapy response and prognosis of patients with advanced NSCLC. Cell Physiol Biochem 2014;34:1578-1588.
  11. Chen J, Zhao X, Ye Y, Wang Y, Tian J: Estrogen receptor beta-mediated proliferative inhibition and apoptosis in human breast cancer by calycosin and formononetin. Cell Physiol Biochem 2013;32:1790-1797.
  12. Brana I, Berger R, Golan T, Haluska P, Edenfield J, Fiorica J, Stephenson J, Martin LP, Westin S, Hanjani P, Jones MB, Almhanna K, Wenham RM, Sullivan DM, Dalton WS, Gunchenko A, Cheng JD, Siu LL, Gray JE: A parallel-arm phase I trial of the humanised anti-IGF-1R antibody dalotuzumab in combination with the AKT inhibitor MK-2206, the mTOR inhibitor ridaforolimus, or the NOTCH inhibitor MK-0752, in patients with advanced solid tumours. Br J Cancer 2014;111:1932-1944.
  13. Gryko M, Kisluk J, Cepowicz D, Zinczuk J, Kamocki Z, Guzinska-Ustymowicz K, Pryczynicz A, Czyzewska J, Kemona A, Kedra B: Expression of insulin-like growth factor receptor type 1 correlate with lymphatic metastases in human gastric cancer. Pol J Pathol 2014;65:135-140.
  14. Li S, Lei X, Zhang J, Yang H, Liu J, Xu C: Insulin-like growth factor 1 promotes growth of gastric cancer by inhibiting foxo1 nuclear retention. Tumour Biol 2015;10.1007/s13277-015-3096-9
  15. Tamura F, Sato Y, Hirakawa M, Yoshida M, Ono M, Osuga T, Okagawa Y, Uemura N, Arihara Y, Murase K, Kawano Y, Iyama S, Takada K, Hayashi T, Sato T, Miyanishi K, Kobune M, Takimoto R, Kato J: RNAi-mediated gene silencing of ST6GalNAc I suppresses the metastatic potential in gastric cancer cells. Gastric Cancer 2014;10.1007/s10120-014-0454-z
  16. Li H, Li Y, Liu D, Sun H, Liu J: miR-224 is critical for celastrol-induced inhibition of migration and invasion of hepatocellular carcinoma cells. Cell Physiol Biochem 2013;32:448-458.
  17. Plasterk RH: Micro RNAs in animal development. Cell 2006;124:877-881.
  18. Valastyan S, Reinhardt F, Benaich N, Calogrias D, Szasz AM, Wang ZC, Brock JE, Richardson AL, Weinberg RA: A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis. Cell 2009;137:1032-1046.
  19. Hyun S, Lee JH, Jin H, Nam J, Namkoong B, Lee G, Chung J, Kim VN: Conserved MicroRNA miR-8/miR-200 and its target USH/FOG2 control growth by regulating PI3K. Cell 2009;139:1096-1108.
  20. Wang K, Diskin SJ, Zhang H, Attiyeh EF, Winter C, Hou C, Schnepp RW, Diamond M, Bosse K, Mayes PA, Glessner J, Kim C, Frackelton E, Garris M, Wang Q, Glaberson W, Chiavacci R, Nguyen L, Jagannathan J, Saeki N, Sasaki H, Grant SF, Iolascon A, Mosse YP, Cole KA, Li H, Devoto M, McGrady PW, London WB, Capasso M, Rahman N, Hakonarson H, Maris JM: Integrative genomics identifies LMO1 as a neuroblastoma oncogene. Nature 2011;469:216-220.
  21. Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004;116:281-297.
  22. Wang Y, Zhou L, Chen J, Li J, He L, Wu P, Wang M, Tong N, Zhang Z, Fang Y: Association of the 3'UTR FOXO3a polymorphism rs4946936 with an increased risk of childhood acute lymphoblastic leukemia in a Chinese population. Cell Physiol Biochem 2014;34:325-332.
  23. Hernandez W, Grenade C, Santos ER, Bonilla C, Ahaghotu C, Kittles RA: IGF-1 and IGFBP-3 gene variants influence on serum levels and prostate cancer risk in African-Americans. Carcinogenesis 2007;28:2154-2159.
  24. Gu MJ, Bae YK, Choi JH: Clinical significance of insulin-growth factor 1 and insulin-growth factor 1 receptor expression in gastrointestinal stromal tumors. Hepatogastroenterology 2013;60:1383-1386.
    External Resources
  25. Li H, Xu L, Zhao L, Ma Y, Zhu Z, Liu Y, Qu X: Insulin-like growth factor-I induces epithelial to mesenchymal transition via GSK-3beta and ZEB2 in the BGC-823 gastric cancer cell line. Oncol Lett 2015;9:143-148.
ppt logo Download Images (.pptx)


Figures
Thumbnail
Thumbnail
Thumbnail

Tables
Thumbnail
Thumbnail
Thumbnail
Thumbnail

Open Access License / Drug Dosage / Disclaimer

Open Access License: This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.