Skip to main content

Roles of MicroRNAs in Esophageal Squamous Cell Carcinoma Pathogenesis

  • Protocol
  • First Online:
Book cover Esophageal Squamous Cell Carcinoma

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2129))

Abstract

MicroRNAs (miRNAs) are 20–22 nucleotides long single-stranded noncoding RNAs. They regulate gene expression posttranscriptionally by base pairing with the complementary sequences in the 3′-untranslated region of their targeted mRNA. Aberrant expression of miRNAs leads to alterations in the expression of oncogenes and tumor suppressors, thereby affecting cellular growth, proliferation, apoptosis, motility, and invasion capacity of gastrointestinal cells, including cells of esophageal squamous cell carcinoma (ESCC). Thus, alterations in miRNAs expression associated with the pathogenesis and progression of ESCC. In addition, expression profiles of miRNAs correlated with various clinicopathological factors, including pathological stages, histological differentiation, invasion, metastasis of cancer, as well as survival rates and therapy response of patients with ESCC. Consequently, expression profiles of miRNAs could be useful as diagnostic, prognostic, and prediction biomarkers in ESCC. Herein, we describe the quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and microarray methods for detection and quantitate miRNAs in ESCC. In addition, we summarize the roles of miRNAs in ESCC pathogenesis, progression, and prognosis.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Ambros V (2004) The functions of animal microRNAs. Nature 431:350–355

    Article  CAS  PubMed  Google Scholar 

  2. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297

    Article  CAS  PubMed  Google Scholar 

  3. Lee Y, Kim M, Han J, Yeom KH, Lee S, Baek SH, Kim VN (2004) MicroRNA genes are transcribed by RNA polymerase II. EMBO J 23:4051–4060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Bernstein E, Caudy AA, Hammond SM, Hannon GJ (2001) Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 409:363–366

    Article  CAS  PubMed  Google Scholar 

  5. Rana TM (2007) Illuminating the silence: understanding the structure and function of small RNAs. Nat Rev Mol Cell Biol 8:23–36

    Article  CAS  PubMed  Google Scholar 

  6. Pratt AJ, MacRae IJ (2009) The RNA-induced silencing complex: a versatile gene-silencing machine. J Biol Chem 284:17897–17901

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, Bartel DP, Linsley PS, Johnson JM (2005) Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 433:769–773

    Article  CAS  PubMed  Google Scholar 

  8. He L, Hannon GJ (2004) MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 5:522–531

    Article  CAS  PubMed  Google Scholar 

  9. Alvarez-Garcia I, Miska EA (2005) MicroRNA functions in animal development and human disease. Development 132:4653–4662

    Article  CAS  PubMed  Google Scholar 

  10. Xiao C, Rajewsky K (2009) MicroRNA control in the immune system: basic principles. Cell 136:26–36

    Article  CAS  PubMed  Google Scholar 

  11. Song JH, Meltzer SJ (2012) MicroRNAs in pathogenesis, diagnosis, and treatment of gastroesophageal cancers. Gastroenterology 143:35–47.e2

    Article  CAS  PubMed  Google Scholar 

  12. Guo Y, Chen Z, Zhang L, Zhou F, Shi S, Feng X, Li B, Meng X, Ma X, Luo M, Shao K, Li N, Qiu B, Mitchelson K, Cheng J, He J (2008) Distinctive microRNA profiles relating to patient survival in esophageal squamous cell carcinoma. Cancer Res 68:26–33

    Article  CAS  PubMed  Google Scholar 

  13. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR (2005) MicroRNA expression profiles classify human cancers. Nature 435:834–838

    Article  CAS  PubMed  Google Scholar 

  14. Islam F, Gopalan V, Law S, Tang JC, Chan KW, Lam AK (2017) MiR-498 in esophageal squamous cell carcinoma: clinicopathological impacts and functional interactions. Hum Pathol 62:141–151

    Article  CAS  PubMed  Google Scholar 

  15. Gopalan V, Islam F, Pillai S, Tang JC, Tong DK, Law S, Chan KW, Lam AK (2016) Overexpression of microRNA-1288 in oesophageal squamous cell carcinoma. Exp Cell Res 348:146–154

    Article  CAS  PubMed  Google Scholar 

  16. Harada K, Baba Y, Ishimoto T, Shigaki H, Kosumi K, Yoshida N, Watanabe M, Baba H (2016) The role of microRNA in esophageal squamous cell carcinoma. J Gastroenterol 51:520–530

    Article  CAS  PubMed  Google Scholar 

  17. Mei LL, Qiu YT, Zhang B, Shi ZZ (2017) MicroRNAs in esophageal squamous cell carcinoma: potential biomarkers and therapeutic targets. Cancer Biomark 19:1–9

    Article  CAS  PubMed  Google Scholar 

  18. Matsushima K, Isomoto H, Kohno S, Nakao K (2010) MicroRNAs and esophageal squamous cell carcinoma. Digestion 82:138–144

    Article  CAS  PubMed  Google Scholar 

  19. Chu Y, Zhu H, Lv L, Zhou Y, Huo J (2013) MiRNA s in oesophageal squamous cancer. Neth J Med 71:69–75

    CAS  PubMed  Google Scholar 

  20. Fu HL, Wu DP, Wang XF, Wang JG, Jiao F, Song LL, Xie H, Wen XY, Shan HS, Du YX, Zhao YP (2013) Altered miRNA expression is associated with differentiation, invasion, and metastasis of esophageal squamous cell carcinoma (ESCC) in patients from Huaian, China. Cell Biochem Biophys 67:657–668

    Article  CAS  PubMed  Google Scholar 

  21. Liu R, Liao J, Yang M, Sheng J, Yang H, Wang Y, Pan E, Guo W, Pu Y, Kim SJ, Yin L (2012) The cluster of miR-143 and miR-145 affects the risk for esophageal squamous cell carcinoma through co-regulating fascin homolog 1. PLoS One 7:e33987

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Hezova R, Kovarikova A, Srovnal J, Zemanova M, Harustiak T, Ehrmann J, Hajduch M, Svoboda M, Sachlova M, Slaby O (2015) Diagnostic and prognostic potential of miR-21, miR-29c, miR-148 and miR-203 in adenocarcinoma and squamous cell carcinoma of esophagus. Diagn Pathol 10:42

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Akagi I, Miyashita M, Ishibashi O, Mishima T, Kikuchi K, Makino H, Nomura T, Hagiwara N, Uchida E, Takizawa T (2011) Relationship between altered expression levels of MIR21, MIR143, MIR145, and MIR205 and clinicopathologic features of esophageal squamous cell carcinoma. Dis Esophagus 24:523–530

    Article  CAS  PubMed  Google Scholar 

  24. Li P, Mao WM, Zheng ZG, Dong ZM, Ling ZQ (2013) Down-regulation of PTEN expression modulated by dysregulated miR-21 contributes to the progression of esophageal cancer. Dig Dis Sci 58:3483–3493

    Article  CAS  PubMed  Google Scholar 

  25. Wang N, Zhang CQ, He JH, Duan XF, Wang YY, Ji X, Zang WQ, Li M, Ma YY, Wang T, Zhao GQ (2013) MiR-21 down-regulation suppresses cell growth, invasion and induces cell apoptosis by targeting FASL, TIMP3, and RECK genes in esophageal carcinoma. Dig Dis Sci 58:1863–1870

    Article  CAS  PubMed  Google Scholar 

  26. Chen G, Peng J, Zhu W, Tao G, Song Y, Zhou X, Wang W (2014) Combined downregulation of microRNA-133a and microRNA-133b predicts chemosensitivity of patients with esophageal squamous cell carcinoma undergoing paclitaxel-based chemotherapy. Med Oncol 31:263

    Article  CAS  PubMed  Google Scholar 

  27. Chen ZL, Zhao XH, Wang JW, Li BZ, Wang Z, Sun J, Tan FW, Ding DP, Xu XH, Zhou F, Tan XG, Hang J, Shi SS, Feng XL, He J (2011) microRNA-92a promotes lymph node metastasis of human esophageal squamous cell carcinoma via E-cadherin. J Biol Chem 286:10725–10734

    Article  CAS  PubMed  Google Scholar 

  28. Hong L, Han Y, Zhang H, Li M, Gong T, Sun L, Wu K, Zhao Q, Fan D (2010) The prognostic and chemotherapeutic value of miR-296 in esophageal squamous cell carcinoma. Ann Surg 251:1056–1063

    Article  PubMed  Google Scholar 

  29. Matsushima K, Isomoto H, Yamaguchi N, Inoue N, Machida H, Nakayama T, Hayashi T, Kunizaki M, Hidaka S, Nagayasu T, Nakashima M, Ujifuku K, Mitsutake N, Ohtsuru A, Yamashita S, Korpal M, Kang Y, Gregory PA, Goodall GJ, Kohno S, Nakao K (2011) MiRNA-205 modulates cellular invasion and migration via regulating zinc finger E-box binding homeobox 2 expression in esophageal squamous cell carcinoma cells. J Transl Med 9:30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Zhang M, Zhou S, Zhang L, Zhang J, Cai H, Zhu J, Huang C, Wang J (2012) miR-518b is down-regulated, and involved in cell proliferation and invasion by targeting Rap1b in esophageal squamous cell carcinoma. FEBS Lett 586:3508–3521

    Article  CAS  PubMed  Google Scholar 

  31. Akanuma N, Hoshino I, Akutsu Y, Murakami K, Isozaki Y, Maruyama T, Yusup G, Qin W, Toyozumi T, Takahashi M, Suito H, Hu X, Sekino N, Matsubara H (2014) MicroRNA-133a regulates the mRNAs of two invadopodia-related proteins, FSCN1 and MMP14, in esophageal cancer. Br J Cancer 110:189–198

    Article  CAS  PubMed  Google Scholar 

  32. Huang SD, Yuan Y, Zhuang CW, Li BL, Gong DJ, Wang SG, Zeng ZY, Cheng HZ (2012) MicroRNA-98 and microRNA-214 post-transcriptionally regulate enhancer of zeste homolog 2 and inhibit migration and invasion in human esophageal squamous cell carcinoma. Mol Cancer 11:51

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Xu X, Chen Z, Zhao X, Wang J, Ding D, Wang Z, Tan F, Tan X, Zhou F, Sun J, Sun N, Gao Y, Shao K, Li N, Qiu B, He J (2012) MicroRNA-25 promotes cell migration and invasion in esophageal squamous cell carcinoma. Biochem Biophys Res Commun 421:640–645

    Article  CAS  PubMed  Google Scholar 

  34. Yokobori T, Suzuki S, Tanaka N, Inose T, Sohda M, Sano A, Sakai M, Nakajima M, Miyazaki T, Kato H, Kuwano H (2013) MiR-150 is associated with poor prognosis in esophageal squamous cell carcinoma via targeting the EMT inducer ZEB1. Cancer Sci 104:48–54

    Article  CAS  PubMed  Google Scholar 

  35. Sun J, Chen Z, Tan X, Zhou F, Tan F, Gao Y, Sun N, Xu X, Shao K, He J (2013) MicroRNA-99a/100 promotes apoptosis by targeting mTOR in human esophageal squamous cell carcinoma. Med Oncol 30:411

    Article  PubMed  CAS  Google Scholar 

  36. Isozaki Y, Hoshino I, Nohata N, Kinoshita T, Akutsu Y, Hanari N, Mori M, Yoneyama Y, Akanuma N, Takeshita N, Maruyama T, Seki N, Nishino N, Yoshida M, Matsubara H (2012) Identification of novel molecular targets regulated by tumor suppressive miR-375 induced by histone acetylation in esophageal squamous cell carcinoma. Int J Oncol 41:985–994

    Article  CAS  PubMed  Google Scholar 

  37. Kong KL, Kwong DL, Chan TH, Law SY, Chen L, Li Y, Qin YR, Guan XY (2012) MicroRNA-375 inhibits tumour growth and metastasis in oesophageal squamous cell carcinoma through repressing insulin-like growth factor 1 receptor. Gut 61:33–42

    Article  CAS  PubMed  Google Scholar 

  38. Liu R, Yang M, Meng Y, Liao J, Sheng J, Pu Y, Yin L, Kim SJ (2013) Tumor-suppressive function of miR-139-5p in esophageal squamous cell carcinoma. PLoS One 8:e77068

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Sun N, Ye L, Chang T, Li X, Li X (2014) microRNA-195-Cdc42 axis acts as a prognostic factor of esophageal squamous cell carcinoma. Int J Clin Exp Pathol 7:6871–6879

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Liu R, Gu J, Jiang P, Zheng Y, Liu X, Jiang X, Huang E, Xiong S, Xu F, Liu G, Ge D, Chu Y (2015) DNMT1-microRNA126 epigenetic circuit contributes to esophageal squamous cell carcinoma growth via ADAM9-EGFR-AKT signaling. Clin Cancer Res 21:854–863

    Article  CAS  PubMed  Google Scholar 

  41. Liu M, Wang Z, Yang S, Zhang W, He S, Hu C, Zhu H, Quan L, Bai J, Xu N (2011) TNF-α is a novel target of miR-19a. Int J Oncol 38:1013–1022

    CAS  PubMed  Google Scholar 

  42. Li H, Zheng D, Zhang B, Liu L, Ou J, Chen W, Xiong S, Gu Y, Yang J (2014) Mir-208 promotes cell proliferation by repressing SOX6 expression in human esophageal squamous cell carcinoma. J Transl Med 12:196

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Harazono Y, Muramatsu T, Endo H, Uzawa N, Kawano T, Harada K, Inazawa J, Kozaki K (2013) miR-655 Is an EMT-suppressive microRNA targeting ZEB1 and TGFBR2. PLoS One 8:e62757

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Liu K, Li L, Rusidanmu A, Wang Y, Lv X (2015) Down-regulation of MiR-1294 is related to dismal prognosis of patients with esophageal squamous cell carcinoma through elevating C-MYC expression. Cell Physiol Biochem 36:100–110

    Article  PubMed  CAS  Google Scholar 

  45. Song Y, Li J, Zhu Y, Dai Y, Zeng T, Liu L, Li J, Wang H, Qin Y, Zeng M, Guan XY, Li Y (2014) MicroRNA-9 promotes tumor metastasis via repressing E-cadherin in esophageal squamous cell carcinoma. Oncotarget 5:11669–11680

    PubMed  PubMed Central  Google Scholar 

  46. Wang XC, Zhang ZB, Wang YY, Wu HY, Li DG, Meng AM, Fan FY (2013) Increased miRNA-22 expression sensitizes esophageal squamous cell carcinoma to irradiation. J Radiat Res 54:401–408

    Article  CAS  PubMed  Google Scholar 

  47. Zhang HF, Zhang K, Liao LD, Li LY, Du ZP, Wu BL, Wu JY, Xu XE, Zeng FM, Chen B, Cao HH, Zhu MX, Dai LH, Long L, Wu ZY, Lai R, Xu LY, Li EM (2014) miR-200b suppresses invasiveness and modulates the cytoskeletal and adhesive machinery in esophageal squamous cell carcinoma cells via targeting Kindlin-2. Carcinogenesis 35:292–301

    Article  PubMed  CAS  Google Scholar 

  48. Lin C, Liu A, Zhu J, Zhang X, Wu G, Ren P, Wu J, Li M, Li J, Song L (2014) miR-508 sustains phosphoinositide signalling and promotes aggressive phenotype of oesophageal squamous cell carcinoma. Nat Commun 5:4620

    Article  CAS  PubMed  Google Scholar 

  49. Zhao Y, Schetter AJ, Yang GB, Nguyen G, Mathé EA, Li P, Cai H, Yu L, Liu F, Hang D, Yang H, Wang XW, Ke Y, Harris CC (2013) microRNA and inflammatory gene expression as prognostic marker for overall survival in esophageal squamous cell carcinoma. Int J Cancer 132:2901–2909

    Article  CAS  PubMed  Google Scholar 

  50. Ge C, Wu S, Wang W, Liu Z, Zhang J, Wang Z, Li R, Zhang Z, Li Z, Dong S, Wang Y, Xue Y, Yang J, Tan Q, Wang Z, Song X (2015) miR-942 promotes cancer stem cell-like traits in esophageal squamous cell carcinoma through activation of Wnt/β-catenin signalling pathway. Oncotarget 6:10964–10977

    PubMed  PubMed Central  Google Scholar 

  51. Zhou S, Yang B, Zhao Y, Xu S, Zhang H, Li Z (2014) Prognostic value of microRNA-100 in esophageal squamous cell carcinoma. J Surg Res 192:515–520

    Article  CAS  PubMed  Google Scholar 

  52. Kurashige J, Watanabe M, Iwatsuki M, Kinoshita K, Saito S, Hiyoshi Y, Kamohara H, Baba Y, Mimori K, Baba H (2012) Overexpression of microRNA-223 regulates the ubiquitin ligase FBXW7 in oesophageal squamous cell carcinoma. Br J Cancer 106:182–188

    Article  CAS  PubMed  Google Scholar 

  53. Xu XL, Jiang YH, Feng JG, Su D, Chen PC, Mao WM (2014) MicroRNA-17, microRNA-18a, and microRNA-19a are prognostic indicators in esophageal squamous cell carcinoma. Ann Thorac Surg 97:1037–1045

    Article  PubMed  Google Scholar 

  54. Lin RJ, Xiao DW, Liao LD, Chen T, Xie ZF, Huang WZ, Wang WS, Jiang TF, Wu BL, Li EM, Xu LY (2012) MiR-142-3p as a potential prognostic biomarker for esophageal squamous cell carcinoma. J Surg Oncol 105:175–182

    Article  CAS  PubMed  Google Scholar 

  55. Zhang M, Yang Q, Zhang L, Zhou S, Ye W, Yao Q, Li Z, Huang C, Wen Q, Wang J (2014) miR-302b is a potential molecular marker of esophageal squamous cell carcinoma and functions as a tumor suppressor by targeting ErbB4. J Exp Clin Cancer Res 33:10

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alfred K. Lam .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Islam, F., Gopalan, V., Lam, A.K. (2020). Roles of MicroRNAs in Esophageal Squamous Cell Carcinoma Pathogenesis. In: Lam, A. (eds) Esophageal Squamous Cell Carcinoma. Methods in Molecular Biology, vol 2129. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0377-2_18

Download citation

  • DOI: https://doi.org/10.1007/978-1-0716-0377-2_18

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-0376-5

  • Online ISBN: 978-1-0716-0377-2

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics