Skip to main content

Advertisement

SpringerLink
Log in

c-Myc induced the regulation of long non-coding RNA RHPN1-AS1 on breast cancer cell proliferation via inhibiting P53

  • Original Article
  • Published:
Molecular Genetics and Genomics Aims and scope Submit manuscript

Abstract

The global burden of breast cancer has been increasing, the mechanism of which is related to multifactorial accumulation of gene mutations. Dysregulation of long noncoding RNA (LncRNA) has been linked to multiple kinds of tumorigenesis. We aimed to identify functionally relevant targets of RHPN1 Antisense RNA 1 (RHPN1-AS1) in breast cancer using breast cancer cell line-based model. Quantitative RT-PCR revealed higher expression levels of RHPN1-AS1 in human breast cancer tissues and cell line MCF-7. RHPN1-AS1 was also located in MCF-7 cells by fluorescence in situ hybridization and western blot assays. Knockdown of RHPN1-AS1 delivered by lentivirus system inhibited MCF-7 cell proliferation indicated by the cell proliferation and colony formation assays, and the knockdown of RHPN1-AS1 enhanced P53 protein expression in MCF-7 and MDA-MB-231 cells. In addition, luciferase reporter assay validated that RHPN1-AS1 is a molecular sponge of miR-4261, and direct transcriptional target of c-Myc. RHPN1-AS1 exerts tumorigenesis by regulating P53 expression via MDM2 gene. These findings provide insights into the role and mechanism of action of lncRNA RHPN-AS1 in breast cancer.

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

Similar content being viewed by others

Abbreviations

LncRNA:

Long noncoding RNA

FISH:

Fluorescence in situ hybridization

References

  • Barr AR, Cooper S, Heldt FS, Butera F, Stoy H, Mansfeld J, Novak B, Bakal C (2017) DNA damage during S-phase mediates the proliferation-quiescence decision in the subsequent G1 via p21 expression. Nat Commun 8:14728

    Article  CAS  Google Scholar 

  • Benson EK, Mungamuri SK, Attie O, Kracikova M, Sachidanandam R, Manfredi JJ, Aaronson SA (2014) p53-dependent gene repression through p21 is mediated by recruitment of E2F4 repression complexes. Oncogene 33(30):3959–3969

    Article  CAS  Google Scholar 

  • Bodai BI, Tuso P (2015) Breast cancer survivorship: a comprehensive review of long-term medical issues and lifestyle recommendations. Perm J 19(2):48–79

    Article  Google Scholar 

  • Bradford JR, Cox A, Bernard P, Camp NJ (2016) Consensus analysis of whole transcriptome profiles from two breast cancer patient cohorts reveals long non-coding RNAs associated with intrinsic subtype and the tumour microenvironment. PLoS ONE 11(9):e0163238

    Article  Google Scholar 

  • Cerk S, Schwarzenbacher D, Adiprasito JB, Stotz M, Hutterer GC, Gerger A, Ling H, Calin GA, Pichler M (2016) Current status of long non-coding RNAs in human breast cancer. Int J Mol Sci 17(9):E1485

    Article  Google Scholar 

  • Coughlin SS, Ekwueme DU (2009) Breast cancer as a global health concern. Cancer Epidemiol 33(5):315–318

    Article  Google Scholar 

  • Danforth DN Jr (2016) Genomic changes in normal breast tissue in women at normal risk or at high risk for breast cancer. Breast Cancer 10:109–146

    PubMed  Google Scholar 

  • Dang CV (2012) MYC on the path to cancer. Cell 149(1):22–35

    Article  CAS  Google Scholar 

  • Ellis PA, Lonning PE, Borresen-Dale A, Aas T, Geisler S, Akslen LA, Salter I, Smith IE, Dowsett M (1997) Absence of p21 expression is associated with abnormal p53 in human breast carcinomas. Br J Cancer 76(4):480–485

    Article  CAS  Google Scholar 

  • Gabay M, Li Y, Felsher DW (2014) MYC activation is a hallmark of cancer initiation and maintenance. CSH Perspect Med 4(6):a014201

    Google Scholar 

  • Goff LA, Davila J, Swerdel MR, Moore JC, Cohen RI, Wu H, Sun YE, Hart RP (2009) Ago2 immunoprecipitation identifies predicted microRNAs in human embryonic stem cells and neural precursors. PLoS ONE 4(9):e7192

    Article  Google Scholar 

  • Gupta GP, Massague J (2006) Cancer metastasis: building a framework. Cell 127(4):679–695

    Article  CAS  Google Scholar 

  • Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai MC, Hung T, Argani P, Rinn JL, Wang Y, Brzoska P, Kong B, Li R, West RB, van de Vijver MJ, Sukumar S, Chang HY (2010) Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 464(7291):1071–1076

    Article  CAS  Google Scholar 

  • Haupt Y, Maya R, Kazaz A, Oren M (1997) Mdm2 promotes the rapid degradation of p53. Nature 387(6630):296–299

    Article  CAS  Google Scholar 

  • Haupt S, Vijayakumaran R, Miranda PJ, Burgess A, Lim E, Haupt Y (2017) The role of MDM2 and MDM4 in breast cancer development and prevention. J Mol Cell Biol 9(1):53–61

    Article  CAS  Google Scholar 

  • Huang SK, Luo Q, Peng H, Li J, Zhao M, Wang J, Gu YY, Li Y, Yuan P, Zhao GH, Huang CZ (2018) A panel of serum noncoding RNAs for the diagnosis and monitoring of response to therapy in patients with breast cancer. Med Sci Monitor 24:2476–2488

    Article  CAS  Google Scholar 

  • Jiao G, Huang Q, Hu M, Liang X, Li F, Lan C, Fu W, An Y, Xu B, Zhou J, Xiao J (2017) Therapeutic suppression of miR-4261 attenuates colorectal cancer by targeting MCC. Mol Ther Nucleic Acids 8:36–45

    Article  CAS  Google Scholar 

  • Jin X, Mu P (2015) Targeting breast cancer metastasis. Breast Cancer 9(Suppl 1):23–34

    PubMed  Google Scholar 

  • Kalkat M, De Melo J, Hickman KA, Lourenco C, Redel C, Resetca D, Tamachi A, Tu WB, Penn LZ (2017) MYC deregulation in primary human cancers. Genes 8(6):E151

    Article  Google Scholar 

  • Klinge CM (2018) Non-coding RNAs in breast cancer. Non-coding RNA 4(4):40

    Article  CAS  Google Scholar 

  • Kundu N, Brekman A, Kim JY, Xiao G, Gao C, Bargonetti J (2017) Estrogen-activated MDM2 disrupts mammary tissue architecture through a p53-independent pathway. Oncotarget 8(29):47916–47930

    Article  Google Scholar 

  • Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W, Funke R, Gage D, Harris K, Heaford A, Howland J, Kann L, Lehoczky J, LeVine R, McEwan P, McKernan K, Meldrim J, Mesirov JP, Miranda C, Morris W, Naylor J, Raymond C, Rosetti M, Santos R, Sheridan A, Sougnez C, Stange-Thomann Y, Stojanovic N, Subramanian A, Wyman D, Rogers J, Sulston J, Ainscough R, Beck S, Bentley D, Burton J, Clee C, Carter N, Coulson A, Deadman R, Deloukas P, Dunham A, Dunham I, Durbin R, French L, Grafham D, Gregory S, Hubbard T, Humphray S, Hunt A, Jones M, Lloyd C, McMurray A, Matthews L, Mercer S, Milne S, Mullikin JC, Mungall A, Plumb R, Ross M, Shownkeen R, Sims S, Waterston RH, Wilson RK, Hillier LW, McPherson JD, Marra MA, Mardis ER, Fulton LA, Chinwalla AT, Pepin KH, Gish WR, Chissoe SL, Wendl MC, Delehaunty KD, Miner TL, Delehaunty A, Kramer JB, Cook LL, Fulton RS, Johnson DL, Minx PJ, Clifton SW, Hawkins T, Branscomb E, Predki P, Richardson P, Wenning S, Slezak T, Doggett N, Cheng JF, Olsen A, Lucas S, Elkin C, Uberbacher E, Frazier M, Gibbs RA, Muzny DM, Scherer SE, Bouck JB, Sodergren EJ, Worley KC, Rives CM, Gorrell JH, Metzker ML, Naylor SL, Kucherlapati RS, Nelson DL, Weinstock GM, Sakaki Y, Fujiyama A, Hattori M, Yada T, Toyoda A, Itoh T, Kawagoe C, Watanabe H, Totoki Y, Taylor T, Weissenbach J, Heilig R, Saurin W, Artiguenave F, Brottier P, Bruls T, Pelletier E, Robert C, Wincker P, Smith DR, Doucette-Stamm L, Rubenfield M, Weinstock K, Lee HM, Dubois J, Rosenthal A, Platzer M, Nyakatura G, Taudien S, Rump A, Yang H, Yu J, Wang J, Huang G, Gu J, Hood L, Rowen L, Madan A, Qin S, Davis RW, Federspiel NA, Abola AP, Proctor MJ, Myers RM, Schmutz J, Dickson M, Grimwood J, Cox DR, Olson MV, Kaul R, Raymond C, Shimizu N, Kawasaki K, Minoshima S, Evans GA, Athanasiou M, Schultz R, Roe BA, Chen F, Pan H, Ramser J, Lehrach H, Reinhardt R, McCombie WR, de la Bastide M, Dedhia N, Blocker H, Hornischer K, Nordsiek G, Agarwala R, Aravind L, Bailey JA, Bateman A, Batzoglou S, Birney E, Bork P, Brown DG, Burge CB, Cerutti L, Chen HC, Church D, Clamp M, Copley RR, Doerks T, Eddy SR, Eichler EE, Furey TS, Galagan J, Gilbert JG, Harmon C, Hayashizaki Y, Haussler D, Hermjakob H, Hokamp K, Jang W, Johnson LS, Jones TA, Kasif S, Kaspryzk A, Kennedy S, Kent WJ, Kitts P, Koonin EV, Korf I, Kulp D, Lancet D, Lowe TM, McLysaght A, Mikkelsen T, Moran JV, Mulder N, Pollara VJ, Ponting CP, Schuler G, Schultz J, Slater G, Smit AF, Stupka E, Szustakowki J, Thierry-Mieg D, Thierry-Mieg J, Wagner L, Wallis J, Wheeler R, Williams A, Wolf YI, Wolfe KH, Yang SP, Yeh RF, Collins F, Guyer MS, Peterson J, Felsenfeld A, Wetterstrand KA, Patrinos A, Morgan MJ, de Jong P, Catanese JJ, Osoegawa K, Shizuya H, Choi S, Chen YJ, Szustakowki J (2001) Initial sequencing and analysis of the human genome. Nature 409(6822):860–921

    Article  CAS  Google Scholar 

  • Liu X, Xiao ZD, Han L, Zhang J, Lee SW, Wang W, Lee H, Zhuang L, Chen J, Lin HK, Wang J, Liang H, Gan B (2016) LncRNA NBR2 engages a metabolic checkpoint by regulating AMPK under energy stress. Nat Cell Biol 18(4):431–442

    Article  CAS  Google Scholar 

  • Lu L, Yu X, Zhang L, Ding X, Pan H, Wen X, Xu S, Xing Y, Fan J, Ge S, Zhang H, Jia R, Fan X (2017) The long non-coding RNA RHPN1-AS1 promotes uveal melanoma progression. Int J Mol Sci 18(1):E226

    Article  Google Scholar 

  • Mercer TR, Mattick JS (2013) Structure and function of long noncoding RNAs in epigenetic regulation. Nat Struct Mol Biol 20(3):300–307

    Article  CAS  Google Scholar 

  • Orom UA, Shiekhattar R (2013) Long noncoding RNAs usher in a new era in the biology of enhancers. Cell 154(6):1190–1193

    Article  Google Scholar 

  • Prensner JR, Chinnaiyan AM (2011) The emergence of lncRNAs in cancer biology. Cancer Discov 1(5):391–407

    Article  CAS  Google Scholar 

  • Sanchez-Mejias A, Tay Y (2015) Competing endogenous RNA networks: tying the essential knots for cancer biology and therapeutics. J Hematol Oncol 8:30

    Article  Google Scholar 

  • Siegel RL, Miller KD, Jemal A (2017) Cancer statistics, 2017. CA Cancer J Clin 67(1):7–30

    Article  Google Scholar 

  • Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA Cancer J Clin 68(1):7–30

    Article  Google Scholar 

  • Wong N, Wang X (2015) miRDB: an online resource for microRNA target prediction and functional annotations. Nucleic Acids Res 43(Database issue):D146–D152

    Article  CAS  Google Scholar 

  • Xu S, Kong D, Chen Q, Ping Y, Pang D (2017) Oncogenic long noncoding RNA landscape in breast cancer. Mol Cancer 16(1):129

    Article  Google Scholar 

  • Zhang P, Cao L, Fan P, Mei Y, Wu M (2016) LncRNA-MIF, a c-Myc-activated long non-coding RNA, suppresses glycolysis by promoting Fbxw7-mediated c-Myc degradation. EMBO Rep 17(8):1204–1220

    Article  CAS  Google Scholar 

Download references

Funding

None.

Author information

Authors and Affiliations

  1. Heze Municipal Hospital, No. 2888 Caozhou Road, Heze, 274031, Shandong, China

    Pei Zhu, Yan Li, Ping Li, Yuying Zhang & Xiaowei Wang

Authors
  1. Pei Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ping Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuying Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiaowei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xiaowei Wang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human participants and/or animals

All applicable international, national, and/or institutional guidelines for the care were followed.

Informed consent

Written consent has derived from each participant.

Additional information

Communicated by S. Hohmann.

Publisher's Note

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

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 86 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhu, P., Li, Y., Li, P. et al. c-Myc induced the regulation of long non-coding RNA RHPN1-AS1 on breast cancer cell proliferation via inhibiting P53. Mol Genet Genomics 294, 1219–1229 (2019). https://doi.org/10.1007/s00438-019-01572-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00438-019-01572-w

Keywords

Search

Navigation