Skip to main content

Advertisement

SpringerLink
Log in

Dysregulation of miR-204-3p Driven by the Viability and Motility of Retinoblastoma via Wnt/β-catenin Pathway In Vitro and In Vivo

  • Original Article
  • Published:
Pathology & Oncology Research

Abstract

Retinoblastoma (RB) is a malignant intraocular tumor that frequently occurs in infants and toddlers. Although the most of RB patients in the developed countries could survival from this cancer, the patients in undeveloped areas are still suffering. The human retinal pigment epithelial cell line ARPE-19 and human retinoblastoma (RB) cell lines HXO-RB44, Y79, and WERI-Rb1 were cultured. The mRNA levels of BANCR and miR-204-3p in these cell lines were measured by qRT-PCR. After transfection with sh-BANCR or treatment with miR-204-3p inhibitor in Y79 cells, the cell proliferation rate, growth, invasion, migration, apoptosis and Wnt/β-catenin signaling pathway activity were measured. The regular Y79 and Y79 cells stably expressed sh-BANCR were injected subcutaneously into nude mice, respectively. The volumes and pathohistological futures of tumors were compared. The biochemical features similar to the cell culture were detected and compered. The mRNA measurements showed that BANCR negatively modulate miR-204-3p expression via directly integration with it. Besides, miR-204-3p and Wnt/β-catenin signalling pathway were found to participate in the oncogenic effects of BANCR on RB cell line by Hoechst staining, cell Counting Kit-8 (CCK-8) assay, wound healing assay, transwell assay, and Western blot analysis in vitro. In addition, an in vivo tumorigenesis experiment in nude mice injected with Y79 cells stably expressed sh-BANCR conformed in the effects of BANCR on RB. Taken together, the knockdown of BANCR inhibited cell proliferation, apoptosis, invasion, and migration in RB via targeting miR-204-3p, the mechanism may involve inhibiting Wnt/β-catenin signaling pathway.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Mendoza PR, Grossniklaus HE (2015) The biology of retinoblastoma. Prog Mol Biol Transl Sci 134:503–516. https://doi.org/10.1016/bs.pmbts.2015.06.012

    Article  CAS  PubMed  Google Scholar 

  2. Rodriguez-Galindo C, Orbach DB, VanderVeen D (2015) Retinoblastoma. Pediatr Clin N Am 62:201–223. https://doi.org/10.1016/j.pcl.2014.09.014

    Article  Google Scholar 

  3. Fabian ID, Onadim Z, Karaa E, Duncan C, Chowdhury T, Scheimberg I, Ohnuma SI, Reddy MA, Sagoo MS (2018) The management of retinoblastoma. Oncogene 37:1551–1560. https://doi.org/10.1038/s41388-017-0050-x

    Article  CAS  PubMed  Google Scholar 

  4. Metz KA, Westerwick D, Driever F, Schmid KW, Le Guin CHD (2017) Retinoblastoma and retinocytoma (retinoma). Pathologe 38:507–514. https://doi.org/10.1007/s00292-017-0384-8

    Article  CAS  PubMed  Google Scholar 

  5. Kivela TT, Hadjistilianou T (2017) Neonatal Retinoblastoma. Asia Pac J Oncol Nurs 4:197–204. https://doi.org/10.4103/apjon.apjon_18_17

    Article  PubMed  PubMed Central  Google Scholar 

  6. Manjandavida FP, Honavar SG, Shields CL, Shields JA (2013) Retinoblastoma: recent update and management Frontiers. Asia Pac J Ophthalmol (Phila) 2:351–353. https://doi.org/10.1097/APO.0000000000000026

    Article  Google Scholar 

  7. Lin P, O'Brien JM (2009) Frontiers in the management of retinoblastoma. Am J Ophthalmol 148:192–198. https://doi.org/10.1016/j.ajo.2009.04.004

    Article  CAS  PubMed  Google Scholar 

  8. Jabbour P, Chalouhi N, Tjoumakaris S, Gonzalez LF, Dumont AS, Chitale R, Rosenwasser R, Bianciotto CG, Shields C (2012) Pearls and pitfalls of intraarterial chemotherapy for retinoblastoma. J Neurosurg Pediatr 10:175–181. https://doi.org/10.3171/2012.5.PEDS1277

    Article  PubMed  Google Scholar 

  9. Gatta G, Capocaccia R, Stiller C, Kaatsch P, Berrino F, Terenziani M, EUROCARE Working Group (2005) Childhood cancer survival trends in Europe: a EUROCARE working group study. J Clin Oncol 23:3742–3751. https://doi.org/10.1200/JCO.2005.00.554

    Article  PubMed  Google Scholar 

  10. Lanzafame M, Bianco G, Terracciano LM, Ng CKY, Piscuoglio S (2018) The role of long non-coding RNAs in Hepatocarcinogenesis. Int J Mol Sci 19. https://doi.org/10.3390/ijms19030682

  11. Clark RJ, Craig MP, Agrawal S, Kadakia M (2018) microRNA involvement in the onset and progression of Barrett's esophagus: a systematic review. Oncotarget 9:8179–8196. https://doi.org/10.18632/oncotarget.24145

    Article  PubMed  PubMed Central  Google Scholar 

  12. Zhou S, Wang L, Yang Q, Liu H, Meng Q, Jiang L, Wang S, Jiang W (2018) Systematical analysis of lncRNA-mRNA competing endogenous RNA network in breast cancer subtypes. Breast Cancer Res Treat 169:267–275. https://doi.org/10.1007/s10549-018-4678-1

    Article  CAS  PubMed  Google Scholar 

  13. Koleckova M, Janikova M, Kolar Z (2018) MicroRNAs in triple-negative breast cancer. Neoplasma 65:1–13. https://doi.org/10.4149/neo_2018_170115N36

    Article  CAS  PubMed  Google Scholar 

  14. Momen-Heravi F, Bala S (2018) Emerging role of non-coding RNA in oral cancer. Cell Signal 42:134–143. https://doi.org/10.1016/j.cellsig.2017.10.009

    Article  CAS  PubMed  Google Scholar 

  15. Li H, Chen S, Liu J, Guo X, Xiang X, Dong T, Ran P, Li Q, Zhu B, Zhang X, Wang D, Xiao C, Zheng S (2018) Long non-coding RNA PVT1-5 promotes cell proliferation by regulating miR-126/SLC7A5 axis in lung cancer. Biochem Biophys Res Commun 495:2350–2355. https://doi.org/10.1016/j.bbrc.2017.12.114

    Article  CAS  PubMed  Google Scholar 

  16. Zhang M, Li Q, Pan Y, Wang H, Liu G, Yin H (2018) MicroRNA-655 attenuates the malignant biological behaviours of retinoblastoma cells by directly targeting PAX6 and suppressing the ERK and p38 MAPK signalling pathways. Oncol Rep 39:2040–2050. https://doi.org/10.3892/or.2018.6264

    Article  CAS  PubMed  Google Scholar 

  17. Wu X, Zeng Y, Wu S, Zhong J, Wang Y, Xu J (2015) MiR-204, down-regulated in retinoblastoma, regulates proliferation and invasion of human retinoblastoma cells by targeting CyclinD2 and MMP-9. FEBS Lett 589:645–650. https://doi.org/10.1016/j.febslet.2015.01.030

    Article  CAS  PubMed  Google Scholar 

  18. Su S, Gao J, Wang T, Wang J, Li H, Wang Z (2015) Long non-coding RNA BANCR regulates growth and metastasis and is associated with poor prognosis in retinoblastoma. Tumour Biol 36:7205–7211. https://doi.org/10.1007/s13277-015-3413-3

    Article  CAS  PubMed  Google Scholar 

  19. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods (San Diego, Calif.) 25:402–408. https://doi.org/10.1006/meth.2001.1262

    Article  CAS  Google Scholar 

  20. Rion N, Ruegg MA (2017) LncRNA-encoded peptides: more than translational noise? Cell Res 27:604–605. https://doi.org/10.1038/cr.2017.35

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Dey BK, Mueller AC, Dutta A (2014) Long non-coding RNAs as emerging regulators of differentiation, development, and disease. Transcription 5:e944014. https://doi.org/10.4161/21541272.2014.944014

    Article  PubMed  PubMed Central  Google Scholar 

  22. Deng H, Zhang J, Shi J, Guo Z, He C, Ding L, Tang JH, Hou Y (2016) Role of long non-coding RNA in tumor drug resistance. Tumour Biol 37:11623–11631. https://doi.org/10.1007/s13277-016-5125-8

    Article  CAS  PubMed  Google Scholar 

  23. Vikram R, Ramachandran R, Abdul KS (2014) Functional significance of long non-coding RNAs in breast cancer. Breast Cancer 21:515–521. https://doi.org/10.1007/s12282-014-0554-y

    Article  PubMed  Google Scholar 

  24. Osielska MA, Jagodzinski PP (2018) Long non-coding RNA as potential biomarkers in non-small-cell lung cancer: what do we know so far? Biomed Pharmacother 101:322–333. https://doi.org/10.1016/j.biopha.2018.02.099

    Article  CAS  PubMed  Google Scholar 

  25. Zhuang J, He S, Wang G, Wang G, Ni J, Zhang S, Ye Y, Xia W (2018) Long non-coding RNA FGFR3-AS1 promotes hepatocellular carcinoma carcinogenesis via modulating PI3K/AKT pathway. Oncol Res 26:1257–1265. https://doi.org/10.3727/096504018X15172756878992

    Article  PubMed  PubMed Central  Google Scholar 

  26. Peng Z, Liu C, Wu M (2018) New insights into long noncoding RNAs and their roles in glioma. Mol Cancer 17:61. https://doi.org/10.1186/s12943-018-0812-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Flockhart RJ, Webster DE, Qu K, Mascarenhas N, Kovalski J, Kretz M, Khavari PA (2012) BRAFV600E remodels the melanocyte transcriptome and induces BANCR to regulate melanoma cell migration. Genome Res 22:1006–1014. https://doi.org/10.1101/gr.140061.112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Liu XF, Hao JL, Xie T, Pant OP, Lu CB, Lu CW, Zhou DD (2018) The BRAF activated non-coding RNA: a pivotal long non-coding RNA in human malignancies. Cell Prolif 51:e12449. https://doi.org/10.1111/cpr.12449

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Shen X, Bai Y, Luo B, Zhou X (2017) Upregulation of lncRNA BANCR associated with the lymph node metastasis and poor prognosis in colorectal cancer. Biol Res 50:32. https://doi.org/10.1186/s40659-017-0136-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Liao T, Qu N, Shi RL, Guo K, Ma B, Cao YM, Xiang J, Lu ZW, Zhu YX, Li DS, Ji QH (2017) BRAF-activated LncRNA functions as a tumor suppressor in papillary thyroid cancer. Oncotarget 8:238–247. https://doi.org/10.18632/oncotarget.10825

    Article  PubMed  Google Scholar 

  31. Liu A, Liu S (2016) Noncoding RNAs in growth and death of Cancer cells. Adv Exp Med Biol 927:137–172. https://doi.org/10.1007/978-981-10-1498-7_5 Review

    Article  CAS  PubMed  Google Scholar 

  32. Khorshidi A, Dhaliwal P, Yang BB (2016) Noncoding RNAs in tumor angiogenesis. Adv Exp Med Biol 927:217–241. https://doi.org/10.1007/978-981-10-1498-7_8

    Article  CAS  PubMed  Google Scholar 

  33. Slattery ML, Mullany LE, Sakoda LC, Samowitz WS, Wolff RK, Stevens JR, Herrick JS (2018) Expression of Wnt-signaling pathway genes and their associations with miRNAs in colorectal cancer. Oncotarget 9:6075–6085. https://doi.org/10.18632/oncotarget.23636

    Article  PubMed  Google Scholar 

  34. Wei H, Zhang JJ, Tang QL (2017) MiR-638 inhibits cervical cancer metastasis through Wnt/beta-catenin signaling pathway and correlates with prognosis of cervical cancer patients. Eur Rev Med Pharmacol Sci 21:5587–5593. https://doi.org/10.26355/eurrev_201712_13999

    Article  CAS  PubMed  Google Scholar 

  35. Huang J, He Y, McLeod HL, Xie Y, Xiao D, Hu H, Chen P, Shen L, Zeng S, Yin X, Ge J, Li L, Tang L, Ma J, Chen Z (2017) miR-302b inhibits tumorigenesis by targeting EphA2 via Wnt/ beta-catenin/EMT signaling cascade in gastric cancer. BMC Cancer 17:886. https://doi.org/10.1186/s12885-017-3875-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Krishnamurthy N, Kurzrock R (2018) Targeting the Wnt/beta-catenin pathway in cancer: update on effectors and inhibitors. Cancer Treat Rev 62:50–60. https://doi.org/10.1016/j.ctrv.2017.11.002

    Article  CAS  PubMed  Google Scholar 

  37. Majidinia M, Aghazadeh J, Jahanban-Esfahlani R, Yousefi B (2018) The roles of Wnt/beta-catenin pathway in tissue development and regenerative medicine. J Cell Physiol 233:5598–5612. https://doi.org/10.1002/jcp.26265

    Article  CAS  PubMed  Google Scholar 

  38. Peng Y, Zhang X, Feng X, Fan X, Jin Z (2017) The crosstalk between microRNAs and the Wnt/beta-catenin signaling pathway in cancer. Oncotarget 8:14089–14106. https://doi.org/10.18632/oncotarget.12923

    Article  PubMed  Google Scholar 

  39. Onyido EK, Sweeney E, Nateri AS (2016) Wnt-signalling pathways and microRNAs network in carcinogenesis: experimental and bioinformatics approaches. Mol Cancer 15:56. https://doi.org/10.1186/s12943-016-0541-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Zhang K, Zhang J, Han L, Pu P, Kang C (2012) Wnt/beta-catenin signaling in glioma. J NeuroImmune Pharmacol 7:740–749. https://doi.org/10.1007/s11481-012-9359-y

    Article  PubMed  Google Scholar 

  41. He H, Chen K, Wang F, Zhao L, Wan X, Wang L, Mo Z (2015) miR-204-5p promotes the adipogenic differentiation of human adipose-derived mesenchymal stem cells by modulating DVL3 expression and suppressing Wnt/beta-catenin signaling. Int J Mol Med 35:1587–1595. https://doi.org/10.3892/ijmm.2015.2160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Wang L, Tian H, Yuan J, Wu H, Wu J, Zhu X (2015) CONSORT: Sam68 is directly regulated by MiR-204 and promotes the self-renewal potential of breast Cancer cells by activating the Wnt/Beta-catenin signaling pathway. Medicine (Baltimore) 94:e2228. https://doi.org/10.1097/MD.0000000000002228

    Article  Google Scholar 

  43. Zou Y, Li J, Chen Y, Xiao H, Zhang F, Yu D, Luo K (2017) BANCR: a novel oncogenic long non-coding RNA in human cancers. Oncotarget 8:94997–95004. https://doi.org/10.18632/oncotarget.22031

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors would like to thank the members of The Second Clinical Medical College of Qingdao University, for providing helpful discussions and technical support concerning the present study.

Author information

Authors and Affiliations

  1. Department of Ophthalmology, The Second Clinical Medical College of Qingdao University, Qingdao, China

    Qing-Xiu Sun, Rong-Rong Wang, Na Liu & Chao Liu

  2. The Central Hospital of Qingdao, The Affiliated Central Hospital of Qingdao University, No. 127, Si-Liu South Road, Qingdao, 266000, Shandong Province, China

    Qing-Xiu Sun, Rong-Rong Wang, Na Liu & Chao Liu

Authors
  1. Qing-Xiu Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rong-Rong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Na Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chao Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chao Liu.

Ethics declarations

Competing Interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sun, QX., Wang, RR., Liu, N. et al. Dysregulation of miR-204-3p Driven by the Viability and Motility of Retinoblastoma via Wnt/β-catenin Pathway In Vitro and In Vivo. Pathol. Oncol. Res. 26, 1549–1558 (2020). https://doi.org/10.1007/s12253-019-00722-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12253-019-00722-0

Keywords

Search

Navigation