MicroRNA-374a Expression as a Prognostic Biomarker in Lung Adenocarcinoma

  • Kim, Yeseul (Department of Pathology, Hanyang University College of Medicine) ;
  • Sim, Jongmin (Department of Pathology, Samsung Medical Center) ;
  • Kim, Hyunsung (Department of Pathology, Hanyang University College of Medicine) ;
  • Bang, Seong Sik (Department of Pathology, Hanyang University College of Medicine) ;
  • Jee, Seungyun (Department of Pathology, Hanyang University College of Medicine) ;
  • Park, Sungeon (Department of Pathology, Hanyang University College of Medicine) ;
  • Jang, Kiseok (Department of Pathology, Hanyang University College of Medicine)
  • Received : 2019.07.17
  • Accepted : 2019.10.01
  • Published : 2019.11.15


Background: Lung cancer is the most common cause of cancer-related death, and adenocarcinoma is the most common histologic subtype. MicroRNA is a small non-coding RNA that inhibits multiple target gene expression at the post-transcriptional level and is commonly dysregulated in malignant tumors. The purpose of this study was to analyze the expression of microRNA-374a (miR-374a) in lung adenocarcinoma and correlate its expression with various clinicopathological characteristics. Methods: The expression level of miR-374a was measured in 111 formalin-fixed paraffin-embedded lung adenocarcinoma tissues using reverse transcription-quantitative polymerase chain reaction assays. The correlation between miR-374a expression and clinicopathological parameters, including clinical outcome, was further analyzed. Results: High miR-374 expression was correlated with advanced pT category (chi-square test, p=.004) and pleural invasion (chi-square test, p=.034). Survival analysis revealed that patients with high miR-374a expression had significantly shorter disease-free survival relative to those with low miR-374a expression (log-rank test, p=.032). Conclusions: miR-374a expression may serve as a potential prognostic biomarker for predicting recurrence in early stage lung adenocarcinoma after curative surgery.


  1. Cronin KA, Lake AJ, Scott S, et al. Annual report to the nation on the status of cancer, part I: national cancer statistics. Cancer 2018; 124: 2785-800.
  2. Kim HC, Jung CY, Cho DG, et al. Clinical characteristics and prognostic factors of lung cancer in Korea: a pilot study of data from the Korean Nationwide Lung Cancer Registry. Tuberc Respir Dis 2019; 82: 118-25.
  3. Chen K, Rajewsky N. The evolution of gene regulation by transcription factors and microRNAs. Nat Rev Genet 2007; 8: 93-103.
  4. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004; 116: 281-97.
  5. Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer 2006; 6: 857-66.
  6. Trang P, Weidhaas JB, Slack FJ. MicroRNAs as potential cancer therapeutics. Oncogene 2008; 27 Suppl 2: S52-7.
  7. Lu T, Zhang C, Chai MX, An YB, Jia JL. MiR-374a promotes the proliferation of osteosarcoma cell proliferation by targeting Axin2. Int J Clin Exp Pathol 2015; 8: 10776-83.
  8. Wang Y, Xin H, Han Z, Sun H, Gao N, Yu H. MicroRNA-374a promotes esophageal cancer cell proliferation via Axin2 suppression. Oncol Rep 2015; 34: 1988-94.
  9. Cai J, Guan H, Fang L, et al. MicroRNA-374a activates $Wnt/{\beta}$-catenin signaling to promote breast cancer metastasis. J Clin Invest 2013; 123: 566-79.
  10. Li H, Chen H, Wang H, et al. MicroRNA-374a promotes hepatocellular carcinoma cell proliferation by targeting mitogen-inducible gene 6 (MIG-6). Oncol Res 2018; 26: 557-63.
  11. Zhang J, He Y, Yu Y, et al. Upregulation of miR-374a promotes tumor metastasis and progression by downregulating LACTB and predicts unfavorable prognosis in breast cancer. Cancer Med 2018 May 23 [Epub].
  12. Ma L, Shao Z, Zhao Y. MicroRNA-374a promotes pancreatic cancer cell proliferation and epithelial to mesenchymal transition by targeting SRCIN1. Pathol Res Pract 2019; 215: 152382.
  13. Son D, Kim Y, Lim S, et al. MiR-374a-5p promotes tumor progression by targeting ARRB1 in triple negative breast cancer. Cancer Lett 2019; 454: 224-33.
  14. Chen Y, Jiang J, Zhao M, et al. MicroRNA-374a suppresses colon cancer progression by directly reducing CCND1 to inactivate the PI3K/AKT pathway. Oncotarget 2016; 7: 41306-19.
  15. Qian D, Chen K, Deng H, et al. MicroRNA-374b suppresses proliferation and promotes apoptosis in T-cell lymphoblastic lymphoma by repressing AKT1 and Wnt-16. Clin Cancer Res 2015; 21: 4881-91.
  16. Zhao M, Xu P, Liu Z, et al. Dual roles of miR-374a by modulated c-Jun respectively targets CCND1-inducing PI3K/AKT signal and PTEN-suppressing $Wnt/{\beta}$-catenin signaling in non-small-cell lung cancer. Cell Death Dis 2018; 9: 78.
  17. Hall JS, Taylor J, Valentine HR, et al. Enhanced stability of microRNA expression facilitates classification of FFPE tumour samples exhibiting near total mRNA degradation. Br J Cancer 2012; 107: 684-94.
  18. Zhang X, Chen J, Radcliffe T, Lebrun DP, Tron VA, Feilotter H. An array-based analysis of microRNA expression comparing matched frozen and formalin-fixed paraffin-embedded human tissue samples. J Mol Diagn 2008; 10: 513-9.
  19. Weng L, Wu X, Gao H, et al. MicroRNA profiling of clear cell renal cell carcinoma by whole-genome small RNA deep sequencing of paired frozen and formalin-fixed, paraffin-embedded tissue specimens. J Pathol 2010; 222: 41-51.
  20. Glud M, Klausen M, Gniadecki R, et al. MicroRNA expression in melanocytic nevi: the usefulness of formalin-fixed, paraffin-embedded material for miRNA microarray profiling. J Invest Dermatol 2009; 129: 1219-24.
  21. Hui AB, Shi W, Boutros PC, et al. Robust global micro-RNA profiling with formalin-fixed paraffin-embedded breast cancer tissues. Lab Invest 2009; 89: 597-606.
  22. Zheng J, Xu T, Chen F, Zhang Y. MiRNA-195-5p functions as a tumor suppressor and a predictive of poor prognosis in non-small cell lung cancer by directly targeting CIAPIN1. Pathol Oncol Res 2019; 25: 1181-90.
  23. Chen Y, Min L, Ren C, et al. MiRNA-148a serves as a prognostic factor and suppresses migration and invasion through Wnt1 in non-small cell lung cancer. PLoS One 2017; 12: e0171751.
  24. Zheng W, Zhao J, Tao Y, et al. MicroRNA-21: a promising biomarker for the prognosis and diagnosis of non-small cell lung cancer. Oncol Lett 2018; 16: 2777-82.
  25. Wang XC, Wang W, Zhang ZB, Zhao J, Tan XG, Luo JC. Overexpression of miRNA-21 promotes radiation-resistance of non-small cell lung cancer. Radiat Oncol 2013; 8: 146.
  26. Gao W, Lu X, Liu L, Xu J, Feng D, Shu Y. MiRNA-21: a biomarker predictive for platinum-based adjuvant chemotherapy response in patients with non-small cell lung cancer. Cancer Biol Ther 2012; 13: 330-40.
  27. He W, Feng L, Xia D, Han N. MiR-374a promotes the proliferation of human osteosarcoma by downregulating FOXO1 expression. Int J Clin Exp Med 2015; 8: 3482-9.
  28. Zhen Y, Fang W, Zhao M, e al. MiR-374a-CCND1-pPI3K/AKT-c-JUN feedback loop modulated by PDCD4 suppresses cell growth, metastasis, and sensitizes nasopharyngeal carcinoma to cisplatin. Oncogene 2017; 36: 275-85.