Skip to main content

Advertisement

SpringerLink
Log in

LncRNA MALAT1 Functions as a Competing Endogenous RNA to Regulate BMI1 Expression by Sponging miR-200c/miR-203 in the Control of the Differentiation of Pulp Cells

  • Original Article
  • Published:
Biochemical Genetics Aims and scope Submit manuscript

Abstract

Background: Long non-coding RNAs (lncRNAs) and miRNAs (microRNAs) are considered as key regulators of several biological processes, including dental development. In this study, we explored the lncRNAs and miRNAs which are involved in dental development. Method: Real-time PCR was performed to identify the candidate lncRNAs and miRNAs involved in dental development. Bioinformatics analysis and luciferase assay were carried out to establish the regulatory relationships between MALAT1, miR-203 and miR-200c in dental development. Results: Among all candidate lncRNAs, only MALAT1 was highly expressed in differentiated human dental pulp cells (hDPCs), and among all candidate miRNAs which are down-regulated in differentiated hDPCs, miR-203, and miR-200c are most decreased. Furthermore, MALAT1 was up-regulated while miR-203 and miR-200c were down-regulated in differentiated hDPCs in a time-dependent manner. MiR-203 and miR-200c were proved to bind to MALAT1. Moreover, BMI1 was identified as a target gene of miR-203 or miR-200c, and BMI1 was time-dependently decreased in hDPCs cultured with odontogenic medium. On the contrary, dentin sialophosphoprotein (DSPP), dentin matrix protein-1 (DMP-1), osteocalcin (OCN), and alkaline phosphatase (ALP), were time-dependently increased in hDPCs cultured with odontogenic medium. Finally, the overexpression of MALAT1 and the knockdown of miR-203/miR-200c both significantly increased the levels of BMI1, DSPP, DMP-1, OCN, and ALP, while the effect of knockdown of miR-203/miR-200c was much stronger than that of the overexpression of MALAT1. Conclusion: Our results demonstrated that MALAT1 functions as a competing endogenous RNA of miR-203 and miR-200c and accordingly promotes BMI1 expression. Therefore, MALAT1 may serve as a biomarker for dental development.

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
Fig. 7

Similar content being viewed by others

Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  • Albuquerque MT, Valera MC, Nakashima M, Nor JE, Bottino MC (2014) Tissue-engineering-based strategies for regenerative endodontics. J Dent Res 93:1222–1231

    Article  CAS  Google Scholar 

  • Alliot-Licht B, Bluteau G, Magne D, Lopez-Cazaux S, Lieubeau B, Daculsi G, Guicheux J (2005) Dexamethasone stimulates differentiation of odontoblast-like cells in human dental pulp cultures. Cell Tissue Res 321:391–400

    Article  CAS  Google Scholar 

  • Atari M, Gil-Recio C, Fabregat M, Garcia-Fernandez D, Barajas M, Carrasco MA, Jung HS, Alfaro FH, Casals N, Prosper F, Ferres-Padro E, Giner L (2012) Dental pulp of the third molar: a new source of pluripotent-like stem cells. J Cell Sci 125:3343–3356

    CAS  PubMed  Google Scholar 

  • Biehs B, Hu JK, Strauli NB, Sangiorgi E, Jung H, Heber RP, Ho S, Goodwin AF, Dasen JS, Capecchi MR, Klein OD (2013) BMI1 represses Ink4a/Arf and Hox genes to regulate stem cells in the rodent incisor. Nat Cell Biol 15:846–852

    Article  CAS  Google Scholar 

  • Burk U, Schubert J, Wellner U, Schmalhofer O, Vincan E, Spaderna S, Brabletz T (2008) A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Rep 9:582–589

    Article  CAS  Google Scholar 

  • Cao H, Wang J, Li X, Florez S, Huang Z, Venugopalan SR, Elangovan S, Skobe Z, Margolis HC, Martin JF, Amendt BA (2010) MicroRNAs play a critical role in tooth development. J Dent Res 89:779–784

    Article  CAS  Google Scholar 

  • Chen W, Xu XK, Li JL, Kong KK, Li H, Chen C, He J, Wang F, Li P, Ge XS, Li FC (2017) MALAT1 is a prognostic factor in glioblastoma multiforme and induces chemoresistance to temozolomide through suppressing miR-203 and promoting thymidylate synthase expression. Oncotarget 8:22783–22799

    Article  Google Scholar 

  • Chiba T, Miyagi S, Saraya A, Aoki R, Seki A, Morita Y, Yonemitsu Y, Yokosuka O, Taniguchi H, Nakauchi H, Iwama A (2008) The polycomb gene product BMI1 contributes to the maintenance of tumor-initiating side population cells in hepatocellular carcinoma. Cancer Res 68:7742–7749

    Article  CAS  Google Scholar 

  • Dimri M, Carroll JD, Cho JH, Dimri GP (2013) microRNA-141 regulates BMI1 expression and induces senescence in human diploid fibroblasts. Cell Cycle 12:3537–3546

    Article  CAS  Google Scholar 

  • Dimri M, Kang M, Dimri GP (2016) A miR-200c/141-BMI1 autoregulatory loop regulates oncogenic activity of BMI1 in cancer cells. Oncotarget 7:36220–36234

    Article  Google Scholar 

  • Gronthos S, Mankani M, Brahim J, Robey PG, Shi S (2000) Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci U S A 97:13625–13630

    Article  CAS  Google Scholar 

  • Hosoya A, Yukita A, Yoshiba K, Yoshiba N, Takahashi M, Nakamura H (2012) Two distinct processes of bone-like tissue formation by dental pulp cells after tooth transplantation. J Histochem Cytochem 60:861–873

    Article  Google Scholar 

  • Ishikawa Y, Ida-Yonemochi H, Suzuki H, Nakakura-Ohshima K, Jung HS, Honda MJ, Ishii Y, Watanabe N, Ohshima H (2010) Mapping of BrdU label-retaining dental pulp cells in growing teeth and their regenerative capacity after injuries. Histochem Cell Biol 134:227–241

    Article  CAS  Google Scholar 

  • Jevnaker AM, Osmundsen H (2008) MicroRNA expression profiling of the developing murine molar tooth germ and the developing murine submandibular salivary gland. Arch Oral Biol 53:629–645

    Article  CAS  Google Scholar 

  • Jin M, Zhang T, Liu C, Badeaux MA, Liu B, Liu R, Jeter C, Chen X, Vlassov AV, Tang DG (2014) miRNA-128 suppresses prostate cancer by inhibiting BMI-1 to inhibit tumor-initiating cells. Cancer Res 74:4183–4195

    Article  CAS  Google Scholar 

  • Kaur P, Tan JR, Karolina DS, Sepramaniam S, Armugam A, Wong PT, Jeyaseelan K (2016) A long non-coding RNA, BC048612 and a microRNA, miR-203 coordinate the gene expression of neuronal growth regulator 1 (NEGR1) adhesion protein. Biochim Biophys Acta 1863:533–543

    Article  CAS  Google Scholar 

  • Kloosterman WP, Plasterk RH (2006) The diverse functions of microRNAs in animal development and disease. Dev Cell 11:441–450

    Article  CAS  Google Scholar 

  • Liao Q, Liu C, Yuan X, Kang S, Miao R, Xiao H, Zhao G, Luo H, Bu D, Zhao H, Skogerbo G, Wu Z, Zhao Y (2011) Large-scale prediction of long non-coding RNA functions in a coding-non-coding gene co-expression network. Nucleic Acids Res 39:3864–3878

    Article  CAS  Google Scholar 

  • Mehrazarin S, Oh JE, Chung CL, Chen W, Kim RH, Shi S, Park NH, Kang MK (2011) Impaired odontogenic differentiation of senescent dental mesenchymal stem cells is associated with loss of Bmi-1 expression. J Endod 37:662–666

    Article  Google Scholar 

  • Ruch JV (1998) Odontoblast commitment and differentiation. Biochem Cell Biol 76:923–938

    Article  CAS  Google Scholar 

  • Ruch JV, Lesot H, Begue-Kirn C (1995) Odontoblast differentiation. Int J Dev Biol 39:51–68

    CAS  PubMed  Google Scholar 

  • Shen B, Yuan Y, Zhang Y, Yu S, Peng W, Huang X, Feng J (2017) Long non-coding RNA FBXL19-AS1 plays oncogenic role in colorectal cancer by sponging miR-203. Biochem Biophys Res Commun 488:67–73

    Article  CAS  Google Scholar 

  • Shimono Y, Zabala M, Cho RW, Lobo N, Dalerba P, Qian D, Diehn M, Liu H, Panula SP, Chiao E, Dirbas FM, Somlo G, Pera RA, Lao K, Clarke MF (2009) Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell 138:592–603

    Article  CAS  Google Scholar 

  • Smith AJ, Cassidy N, Perry H, Begue-Kirn C, Ruch JV, Lesot H (1995) Reactionary dentinogenesis. Int J Dev Biol 39:273–280

    CAS  PubMed  Google Scholar 

  • Song Z, Chen LL, Wang RF, Qin W, Huang SH, Guo J, Lin ZM, Tian YG (2017) MicroRNA-135b inhibits odontoblast-like differentiation of human dental pulp cells by regulating Smad5 and Smad4. Int Endod J 50(7):685–693

    Article  CAS  Google Scholar 

  • Wei J, Zhai L, Xu J, Wang H (2006) Role of Bmi1 in H2A ubiquitylation and Hox gene silencing. J Biol Chem 281:22537–22544

    Article  CAS  Google Scholar 

  • Xiao H, Tang K, Liu P, Chen K, Hu J, Zeng J, Xiao W, Yu G, Yao W, Zhou H, Li H, Pan Y, Li A, Ye Z, Wang J, Xu H, Huang Q (2015) LncRNA MALAT1 functions as a competing endogenous RNA to regulate ZEB2 expression by sponging miR-200s in clear cell kidney carcinoma. Oncotarget 6:38005–38015

    Article  Google Scholar 

  • Xiao JN, Yan TH, Yu RM, Gao Y, Zeng WL, Lu SW, Que HX, Liu ZP, Jiang JH (2017) Long non-coding RNA UCA1 regulates the expression of Snail2 by miR-203 to promote hepatocellular carcinoma progression. J Cancer Res Clin Oncol 143(6):981–990

    Article  CAS  Google Scholar 

  • Yin Y, Xue X, Wang Q, Chen N, Miao D (2016) Bmi1 plays an important role in dentin and mandible homeostasis by maintaining redox balance. Am J Transl Res 8:4716–4725

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Zhou SY, Yan HZ, Xu DD, Chen HX, Wang XY, Wang X, Liu YT, Zhang L, Wang S, Zhou PJ, Fu WY, Ruan BB, Ma DL, Wang Y, Liu QY, Ren Z, Liu Z, Zhang R, Wang YF (2016) miR-203 inhibits proliferation and self-renewal of leukemia stem cells by targeting survivin and Bmi-1. Sci Rep 6:19995

    Article  CAS  Google Scholar 

  • Zheng Y, Jia L (2016) Long noncoding RNAs related to the odontogenic potential of dental mesenchymal cells in mice. Arch Oral Biol 67:1–8

    Article  CAS  Google Scholar 

Download references

Acknowledgements

None

Funding

None.

Author information

Authors and Affiliations

  1. Department of Stomatology, No. 215 Hospital of Shaanxi Nuclear Industry, Xianyang, 712000, Shaanxi, China

    Hong Jin

  2. Department of Stomatology, The Second Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, 712000, Shaanxi, China

    Junhai Zhao

  3. Department of Stomatology, Shenmu City Hospital, No. 61 Hepan Road, Yingbin Road Ave, Shenmu, Yulin, 719300, Shaanxi, China

    Cheng Li

Authors
  1. Hong Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Junhai Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cheng Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

CL and HJ planned the study; HJ and JHZ collected and analyzed the data; HJ and CL composed the manuscript; and all the other co-authors approved the final manuscript.

Corresponding author

Correspondence to Cheng Li.

Ethics declarations

Conflict of interest

None.

Ethical Approval

The institution’s Ethics and Research Committees had already agreed with this study.

Consent for Publication

Not applicable.

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

Jin, H., Zhao, J. & Li, C. LncRNA MALAT1 Functions as a Competing Endogenous RNA to Regulate BMI1 Expression by Sponging miR-200c/miR-203 in the Control of the Differentiation of Pulp Cells. Biochem Genet 59, 1260–1277 (2021). https://doi.org/10.1007/s10528-021-10054-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10528-021-10054-x

Keywords

Search

Navigation