Advertisement

Tumor Biology

, Volume 36, Issue 5, pp 3337–3343 | Cite as

Expression of serum let-7c, let-7i, and let-7f microRNA with its target gene, pepsinogen C, in gastric cancer and precancerous disease

  • Wen-Jing Liu
  • Qian Xu
  • Li-Ping Sun
  • Qi-Guan Dong
  • Cai-yun He
  • Yuan Yuan
Research Article

Abstract

This study examined the expression patterns of serum let-7 microRNA (miRNA) and its target gene, pepsinogen C (PGC), in gastric cancer (GC) and precancerous disease patients to evaluate their diagnostic efficiency for GC and its precursor and to investigate any correlation between the two. Serum samples were taken from 638 patients, including 214 GC patients, 222 atrophic gastritis (AG) patients, and 202 controls (CON). The expression of serum let-7 miRNA was detected in control-AG (precancerous disease) through to GC patients using quantitative reverse-transcription polymerase chain reaction. Serum PGC was determined by enzyme-linked immuno-sorbent assay. PGC expression in situ was detected by immunohistochemistry staining. The luciferase reporter gene system was used to verify correlation between let-7 miRNA and its predicted target gene. The results showed that serum let-7c, let-7i, and let-7f demonstrated significant differences in the CON-AG-GC sequence (P = 0.017, P < 0.001, P = 0.003, respectively); let-7c was significantly lower in the AG group, and let-7i and let-7f were significantly higher in the GC group. Significantly different expressions of serum PGC were found among the three diseases, and also between AG vs. CON, and GC vs. CON (P = 0.027, P = 0.001, respectively). Linear-regression analysis suggested that serum let-7c was negatively correlated to the expression of PGC (r = −0.096, P = 0.047), and serum let-7c, let-7i, and let-7f showed no association with PGC expression in tissue. In addition, serum let-7c, let-7f, and let-7i showed significant correlations with environment factors. Serum let-7c, let-7i, and let-7f demonstrated significant differences in the CON-AG-GC disease sequence indicating that let-7 miRNA might have value by serving as potential biomarker in the diagnosis of GC or its precancerous diseases. There were significant negative correlations between serum let-7c and its target gene PGC expression.

Keywords

miRNA let-7 Pepsinogen Gastric cancer Atrophic gastritis 

Notes

Acknowledgments

This work was supported by grants from the National Key Basic Research Program of China (973 Program ref no. 2010CB529304), the National Natural Science Foundation of China (ref no. 31200968), and the Science Technology Project in Liaoning Province (ref no. 2011225002).

Conflicts of interest

None

References

  1. 1.
    Bartel DP. Micrornas: target recognition and regulatory functions. Cell. 2009;136:215–33.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Alvarez-Garcia I, Miska EA. Microrna functions in animal development and human disease. Development. 2005;132:4653–62.CrossRefPubMedGoogle Scholar
  3. 3.
    Kidner CA, Martienssen RA. The developmental role of microrna in plants. Curr Opin Plant Biol. 2005;8:38–44.CrossRefPubMedGoogle Scholar
  4. 4.
    Ma R, Jiang T, Kang X. Circulating microRNAs in cancer: origin, function and application. J Exp Clin Cancer Res. 2012;31:38.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Li M, Li J, Ding X, He M, Cheng SY. Microrna and cancer. Aaps J. 2010;12:309–17.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Cho WC. Oncomirs: the discovery and progress of micrornas in cancers. Mol Cancer. 2007;6:60.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating micrornas as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008;105:10513–8.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Hatfield S, Ruohola-Baker H. Microrna and stem cell function. Cell Tissue Res. 2008;331:57–66.CrossRefPubMedGoogle Scholar
  9. 9.
    Ruby JG, Jan C, Player C, Axtell MJ, Lee W, Nusbaum C, et al. Large-scale sequencing reveals 21u-rnas and additional micrornas and endogenous sirnas in c. Elegans Cell. 2006;127:1193–207.CrossRefPubMedGoogle Scholar
  10. 10.
    Roush S, Slack FJ. The let-7 family of micrornas. Trends Cell Biol. 2008;18:505–16.CrossRefPubMedGoogle Scholar
  11. 11.
    Schulman BR, Esquela-Kerscher A, Slack FJ. Reciprocal expression of lin-41 and the micrornas let-7 and mir-125 during mouse embryogenesis. Dev Dyn. 2005;234:1046–54.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Esquela-Kerscher A, Slack FJ. Oncomirs—micrornas with a role in cancer. Nat Rev Cancer. 2006;6:259–69.CrossRefPubMedGoogle Scholar
  13. 13.
    Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C, et al. Let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell. 2007;131:1109–23.CrossRefPubMedGoogle Scholar
  14. 14.
    Bussing I, Slack FJ, Grosshans H. Let-7 micrornas in development, stem cells and cancer. Trends Mol Med. 2008;14:400–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Peter ME. Let-7 and mir-200 micrornas: guardians against pluripotency and cancer progression. Cell Cycle. 2009;8:843–52.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Liu Q, Lv GD, Qin X, Gen YH, Zheng ST, Liu T, et al. Role of microrna let-7 and effect to hmga2 in esophageal squamous cell carcinoma. Mol Biol Rep. 2012;39:1239–46.CrossRefPubMedGoogle Scholar
  17. 17.
    Ning PF, Liu HJ, Yuan Y. Dynamic expression of pepsinogen c in gastric cancer, precancerous lesions and helicobacter pylori associated gastric diseases. World J Gastroenterol. 2005;11:2545–8.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Xu Q, Dong QG, Sun LP, He CY, Yuan Y. Expression of serum mir-20a-5p, let-7a, and mir-320a and their correlations with pepsinogen in atrophic gastritis and gastric cancer: a case–control study. BMC Clin Pathol. 2013;13:11.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Wang YT, Tsai PC, Liao YC, Hsu CY, Juo SH: Circulating micrornas have a sex-specific association with metabolic syndrome. J Biomed Sci;20:72.Google Scholar
  20. 20.
    Gandhi R, Healy B, Gholipour T, Egorova S, Musallam A, Hussain MS, Nejad P, Patel B, Hei H, Khoury S, Quintana F, Kivisakk P, Chitnis T, Weiner HL: Circulating micrornas as biomarkers for disease staging in multiple sclerosis. Ann Neurol;73:729–740.Google Scholar
  21. 21.
    Luo X, Zhang H, Xiao J, Wang Z: Regulation of human cardiac ion channel genes by micrornas: Theoretical perspective and pathophysiological implications. Cell Physiol Biochem;25:571–586.Google Scholar
  22. 22.
    Kobayashi E, Satow R, Ono M, Masuda M, Honda K, Sakuma T, Kawai A, Morioka H, Toyama Y, Yamada T: Microrna expression and functional profiles of osteosarcoma. Oncology;86:94–103.Google Scholar
  23. 23.
    Kobayashi M, Salomon C, Tapia J, Illanes SE, Mitchell MD, Rice GE: Ovarian cancer cell invasiveness is associated with discordant exosomal sequestration of let-7 mirna and mir-200. J Transl Med;12:4.Google Scholar
  24. 24.
    Zhao B, Han H, Chen J, Zhang Z, Li S, Fang F, Zheng Q, Ma Y, Zhang J, Wu N, Yang Y: Microrna let-7c inhibits migration and invasion of human non-small cell lung cancer by targeting itgb3 and map4k3. Cancer Lett;342:43–51.Google Scholar
  25. 25.
    Li P, He C, Sun L, Dong N, Yuan Y. Pepsinogen i and ii expressions in situ and their correlations with serum pesignogen levels in gastric cancer and its precancerous disease. BMC Clin Pathol. 2013;13:22.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Xu Q, Sun LP, Wang BG, Liu JW, Li P, He CY, et al. The co-expression of functional gastric proteins in dynamic gastric diseases and its clinical significance. BMC Clin Pathol. 2013;13:21.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    JiangFeng F, Jiu YS, Wen ZZ, Ben L. The expression of fas/fasl and apoptosis in yak placentomes. Anim Reprod Sci. 2011;128:107–16.CrossRefPubMedGoogle Scholar
  28. 28.
    Gu J, Liang Y, Qiao L, Li X, Li X, Lu Y, et al. Expression analysis of uri/rmp gene in endometrioid adenocarcinoma by tissue microarray immunohistochemistry. Int J Clin Exp Pathol. 2013;6:2396–403.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Zhang H, Hao Y, Yang J, Zhou Y, Li J, Yin S, Sun C, Ma M, Huang Y, Xi JJ: Genome-wide functional screening of mir-23b as a pleiotropic modulator suppressing cancer metastasis. Nat Commun;2:554.Google Scholar
  30. 30.
    Aqeilan RI, Calin GA, Croce CM: Mir-15a and mir-16-1 in cancer: Discovery, function and future perspectives. Cell Death Differ;17:215–220.Google Scholar
  31. 31.
    Tang Z, Ow GS, Thiery JP, Ivshina AV, Kuznetsov VA: Meta-analysis of transcriptome reveals let-7b as an unfavorable prognostic biomarker and predicts molecular and clinical subclasses in high-grade serous ovarian carcinoma. Int J CancerGoogle Scholar
  32. 32.
    Wang QZ, Lv YH, Gong YH, Li ZF, Xu W, Diao Y, et al. Double-stranded let-7 mimics, potential candidates for cancer gene therapy. J Physiol Biochem. 2012;68:107–19.CrossRefPubMedGoogle Scholar
  33. 33.
    Liu K, Qian T, Tang L, Wang J, Yang H, Ren J. Decreased expression of microrna let-7i and its association with chemotherapeutic response in human gastric cancer. World J Surg Oncol. 2012;10:225.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Chen Q, Ge X, Zhang Y, Xia H, Yuan D, Tang Q, Chen L, Pang X, Leng W, Bi F: Plasma mir-122 and mir-192 as potential novel biomarkers for the early detection of distant metastasis of gastric cancer. Oncol RepGoogle Scholar
  35. 35.
    Liu R, Zhang C, Hu Z, Li G, Wang C, Yang C, et al. A five-microrna signature identified from genome-wide serum microrna expression profiling serves as a fingerprint for gastric cancer diagnosis. Eur J Cancer. 2011;47:784–91.CrossRefPubMedGoogle Scholar
  36. 36.
    Zhang Y, Fan KJ, Sun Q, Chen AZ, Shen WL, Zhao ZH, Zheng XF, Yang X: Functional screening for mirnas targeting smad4 identified mir-199a as a negative regulator of tgf-beta signalling pathway. Nucleic Acids Res;40:9286–9297.Google Scholar
  37. 37.
    Su Y, Ni Z, Wang G, Cui J, Wei C, Wang J, Yang Q, Xu Y, Li F: Aberrant expression of micrornas in gastric cancer and biological significance of mir-574-3p. Int Immunopharmacol;13:468–475.Google Scholar
  38. 38.
    Liang S, He L, Zhao X, Miao Y, Gu Y, Guo C, et al. Microrna let-7f inhibits tumor invasion and metastasis by targeting myh9 in human gastric cancer. PLoS ONE. 2011;6:e18409.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Nadiminty N, Tummala R, Lou W, Zhu Y, Zhang J, Chen X. Microrna let-7c suppresses androgen receptor expression and activity via regulation of myc expression in prostate cancer cells. J Biol Chem. 2012;287:1527–37.CrossRefPubMedGoogle Scholar
  40. 40.
    Liu C, Kelnar K, Vlassov AV, Brown D, Wang J, Tang DG. Distinct microrna expression profiles in prostate cancer stem/progenitor cells and tumor-suppressive functions of let-7. Cancer Res. 2012;72:3393–404.CrossRefPubMedGoogle Scholar
  41. 41.
    Miki K: Gastric cancer screening by combined assay for serum anti-helicobacter pylori igg antibody and serum pepsinogen levels - "abc method". Proc Jpn Acad Ser B Phys Biol Sci;87:405–414.Google Scholar
  42. 42.
    Badrnya S, Baumgartner R, Assinger A: Smoking alters circulating plasma microvesicle pattern and microrna signatures. Thromb Haemost;112:128–136.Google Scholar
  43. 43.
    Tapocik JD, Barbier E, Flanigan M, Solomon M, Pincus A, Pilling A, Sun H, Schank JR, King C, Heilig M: Microrna-206 in rat medial prefrontal cortex regulates bdnf expression and alcohol drinking. J Neurosci;34:4581–4588.Google Scholar
  44. 44.
    Hayashi Y, Tsujii M, Wang J, Kondo J, Akasaka T, Jin Y, et al. Caga mediates epigenetic regulation to attenuate let-7 expression in helicobacter pylori-related carcinogenesis. Gut. 2013;62:1536–46.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Wen-Jing Liu
    • 1
    • 2
  • Qian Xu
    • 1
  • Li-Ping Sun
    • 1
  • Qi-Guan Dong
    • 1
  • Cai-yun He
    • 1
  • Yuan Yuan
    • 1
  1. 1.Tumor Etiology and Screening Department of Cancer Institute and General Surgery, Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education DepartmentThe First Affiliated Hospital of China Medical UniversityShenyangChina
  2. 2.Department of oncologyLiaoning Cancer Hospital and InstituteShenyangChina

Personalised recommendations