Vol 60, No 3 (2022)
Original paper
Published online: 2022-06-28

open access

Page views 4767
Article views/downloads 864
Get Citation

Connect on Social Media

Connect on Social Media

Serum exosomal microRNA-370-3p and microRNA-196a-5p are potential biomarkers for the diagnosis and prognosis of hepatocellular carcinoma

Yaning Wei1, Qian Zhang1, Lin An1, Guotao Fang1, Dan Hong1, Ting Jiao1, Hua Yang1, Zhiyu Wang1
Pubmed: 35762276
Folia Histochem Cytobiol 2022;60(3):215-225.

Abstract

Introduction. Evidence has shown that some microRNAs (miRNAs) play a role in tumorigenesis of hepatocellular carcinoma (HCC). Herein, we aimed to evaluate the diagnostic and prognostic values of serum exosomal miR-370-3p and miR-196a-5p in patients with HCC.
Material and methods. Serum exosomes in 90 HCC patients were extracted and identified. Serum exosomal miR-370-3p and miR-196a-5p expression in HCC patients were detected. The diagnostic value of miR-370-3p and miR-196a- 5p, relationship between miR-370-3p and miR-196a-5p expression and clinicopathological features and prognosis of patients with HCC were analyzed. Relationship between miR-370-3p and miR-196a-5p expression and liver function indices such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) in HCC patients were analyzed. The effects of miR-370-3p and miR-196a-5p on Huh-7 HCC cells’ proliferation, invasion and migration were determined.
Results. Lower expression of miR-370-3p and higher expression of miR-196a-5p were found in serum exosomes of HCC patients. Serum exosomal miR-370-3p and miR-196a-5p were associated with tumor size, tumor grade and TNM stage as well as prognosis and liver function indices of HCC patients. Overexpressed miR-370-3p or silenced miR-196a-5p suppressed proliferation, invasion and migration of Huh-7 HCC cells.
Conclusions. We suggest that miR-370-3p/miR-196a-5p in serum exosomes of HCC patients could be potential biomarkers for the diagnosis and prognosis of HCC.

Article available in PDF format

View PDF Download PDF file

References

  1. El-Garem H, Ammer A, Shehab H, et al. Circulating microRNA, miR-122 and miR-221 signature in Egyptian patients with chronic hepatitis C related hepatocellular carcinoma. World J Hepatol. 2014; 6(11): 818–824.
  2. El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007; 132(7): 2557–2576.
  3. Liu Wh, Ren Ln, Wang X, et al. Combination of exosomes and circulating microRNAs may serve as a promising tumor marker complementary to alpha-fetoprotein for early-stage hepatocellular carcinoma diagnosis in rats. J Cancer Res Clin Oncol. 2015; 141(10): 1767–1778.
  4. Ghidini M, Braconi C. Non-Coding RNAs in Primary Liver Cancer. Front Med (Lausanne). 2015; 2: 36.
  5. Wang X, Jing G, Zhou B, et al. Identification of prognostic markers for hepatocellular carcinoma based on miRNA expression profiles. Life Sci. 2019; 232: 116596.
  6. Baskaran S, Panner Selvam MK, Agarwal A. Exosomes of male reproduction. Adv Clin Chem. 2020; 95: 149–163.
  7. Yaghoubi Y, Movassaghpour A, Zamani M, et al. Human umbilical cord mesenchymal stem cells derived-exosomes in diseases treatment. Life Sci. 2019; 233: 116733.
  8. Groot M, Lee H. Sorting mechanisms for micrornas into extracellular vesicles and their associated diseases. Cells. 2020; 9(4).
  9. Mjelle R, Dima SO, Bacalbasa N, et al. Comprehensive transcriptomic analyses of tissue, serum, and serum exosomes from hepatocellular carcinoma patients. BMC Cancer. 2019; 19(1): 1007.
  10. Pan XP, Huang LH, Wang X. MiR-370 functions as prognostic marker in patients with hepatocellular carcinoma. Eur Rev Med Pharmacol Sci. 2017; 21(16): 3581–3585.
  11. Wang SY, Chen CL, Hu YC, et al. High expression of microRNA-196a is associated with progression of hepatocellular carcinoma in younger patients. Cancers (Basel). 2019; 11(10).
  12. Sohn W, Kim J, Kang SH, et al. Serum exosomal microRNAs as novel biomarkers for hepatocellular carcinoma. Exp Mol Med. 2015; 47(9): e184.
  13. Xue X, Zhao Y, Wang X, et al. Development and validation of serum exosomal microRNAs as diagnostic and prognostic biomarkers for hepatocellular carcinoma. J Cell Biochem. 2019; 120(1): 135–142.
  14. Jun Li, Yang Gu, Zhisu L. The utility of serum exosomal microRNAs in hepatocellular carcinoma. Biomed Pharmacother. 2019; 111: 1221–1227.
  15. Wang S, Qiu L, Yan X, et al. Loss of microRNA 122 expression in patients with hepatitis B enhances hepatitis B virus replication through cyclin G(1) -modulated P53 activity. Hepatology. 2012; 55(3): 730–741.
  16. Shi Y, Yang X, Xue X, et al. HANR enhances autophagy-associated sorafenib resistance through miR-29b/ATG9A axis in hepatocellular carcinoma. OncoTargets and Therapy. 2020; Volume 13: 2127–2137.
  17. Huang Z, Chen W, Du Y, et al. Serum miR-16 as a potential biomarker for human cancer diagnosis: results from a large-scale population. J Cancer Res Clin Oncol. 2019; 145(3): 787–796.
  18. Tuo YL, Li XM, Luo J. Long noncoding RNA UCA1 modulates breast cancer cell growth and apoptosis through decreasing tumor suppressive miR-143. Eur Rev Med Pharmacol Sci. 2015; 19(18): 3403–3411.
  19. Fu Yu, Cai L, Lei X, et al. Retraction Note to: Circular RNA ABCB10 promotes hepatocellular carcinoma progression by increasing HMG20A expression by sponging miR-670-3p. Cancer Cell International. 2020; 20: 485.
  20. Lin ZH, Jiang JR, Ma XK, et al. Prognostic value of serum HIF-1α change following transarterial chemoembolization in hepatocellular carcinoma. Clin Exp Med. 2021; 21(1): 109–120.
  21. Mu Qi, Najafi M. Resveratrol for targeting the tumor microenvironment and its interactions with cancer cells. Int Immunopharmacol. 2021; 98: 107895.
  22. Mondal P, Kaur B, Natesh J, et al. The emerging role of miRNA in the perturbation of tumor immune microenvironment in chemoresistance: Therapeutic implications. Semin Cell Dev Biol. 2022; 124: 99–113.
  23. Hu S, Ma J, Su C, et al. Engineered exosome-like nanovesicles suppress tumor growth by reprogramming tumor microenvironment and promoting tumor ferroptosis. Acta Biomater. 2021; 135: 567–581.
  24. Yang E, Wang X, Gong Z, et al. Exosome-mediated metabolic reprogramming: the emerging role in tumor microenvironment remodeling and its influence on cancer progression. Signal Transduct Target Ther. 2020; 5(1): 242.
  25. Zhang Xu, Yuan X, Shi H, et al. Exosomes in cancer: small particle, big player. J Hematol Oncol. 2015; 8: 83.
  26. He Y, He X. MicroRNA-370 regulates cellepithelial-mesenchymal transition, migration, invasion, and prognosis of hepatocellular carcinoma by targeting GUCD1. Yonsei Med J. 2019; 60(3): 267–276.
  27. Lin L, Wang D, Qu S. miR-370-3p alleviates ulcerative colitis-related colorectal cancer in mice through inhibiting the inflammatory response and epithelial-mesenchymal transition. Drug Des Devel Ther. 2020; 13: 1127–1141.
  28. Peng Z, Wu T, Li Y, et al. MicroRNA-370-3p inhibits human glioma cell proliferation and induces cell cycle arrest by directly targeting β-catenin. Brain Res. 2016; 1644: 53–61.
  29. Wang H, Yang G, Yu Y, et al. MicroRNA-490-3p suppresses the proliferation and invasion of hepatocellular carcinoma cells via targeting TMOD3. Oncol Lett. 2020; 20(4): 95.
  30. Li X, An M, Gao Z. In hepatocellular carcinoma, miRNA-296-3p targets MSL2 and suppresses cell proliferation and invasion. J Oncol. 2021; 2021: 7430468.
  31. Lulli V, Buccarelli M, Ilari R, et al. MiR-370-3p impairs glioblastoma stem-like cell malignancy regulating a complex interplay between HMGA2/HIF1A and the oncogenic long non-coding RNA (lncrna) NEAT1. Int J Mol Sci. 2020; 21(10).
  32. Chen F, Feng Z, Zhu J, et al. Emerging roles of circRNA_NEK6 targeting miR-370-3p in the proliferation and invasion of thyroid cancer via Wnt signaling pathway. Cancer Biol Ther. 2018; 19(12): 1139–1152.
  33. Zhang R, Wang J, Jia E, et al. lncRNA BCAR4 sponges miR‑370‑3p to promote bladder cancer progression via Wnt signaling. Int J Mol Med. 2020; 45(2): 578–588.
  34. Liu L, Yan C, Tao S, et al. Circ_0058124 aggravates the progression of papillary thyroid carcinoma by activating LMO4 expression via targeting miR-370-3p. Cancer Manag Res. 2020; 12: 9459–9470.
  35. Bao M, Pan S, Yang W. Serum miR-10a-5p and miR-196a-5p as non-invasive biomarkers in non-small cell lung cancer. Int J Clin Exp Pathol. 2018; 11(2): 773–780.
  36. Li HL, Xie SP, Yang YL, et al. Clinical significance of upregulation of mir-196a-5p in gastric cancer and enriched KEGG pathway analysis of target genes. Asian Pac J Cancer Prev. 2015; 16(5): 1781–1787.
  37. Huang G, Li H, Wang J, et al. Combination of tumor suppressor miR-20b-5p, miR-30a-5p, and miR-196a-5p as a serum diagnostic panel for renal cell carcinoma. Pathol Res Pract. 2020; 216(11): 153152.
  38. Miao Ke, Liu SD, Huang WX, et al. MiR-224 executes a tumor accelerative role during hepatocellular carcinoma malignancy by targeting cytoplasmic polyadenylation element-binding protein 3. Pharmacology. 2020; 105(7-8): 477–487.
  39. Xin He, Wang C, Liu Z. miR-196a-5p promotes metastasis of colorectal cancer via targeting IκBα. BMC Cancer. 2019; 19(1): 30.
  40. Pan Y, Shu X, Sun L, et al. miR‑196a‑5p modulates gastric cancer stem cell characteristics by targeting Smad4. Int J Oncol. 2017; 50(6): 1965–1976.
  41. Li S, Zhou J, Wang Z, et al. Long noncoding RNA GAS5 suppresses triple negative breast cancer progression through inhibition of proliferation and invasion by competitively binding miR-196a-5p. Biomed Pharmacother. 2018; 104: 451–457.
  42. Zhao X, Liu Y, Zheng J, et al. GAS5 suppresses malignancy of human glioma stem cells via a miR-196a-5p/FOXO1 feedback loop. Biochim Biophys Acta Mol Cell Res. 2017; 1864(10): 1605–1617.