Skip to main content
Log in

Long non‐coding RNA AGAP2-AS1 promotes proliferation and metastasis in papillary thyroid cancer by miR-628-5p/KLF12 axis

  • Published:
Journal of Bioenergetics and Biomembranes Aims and scope Submit manuscript

Abstract

Long non-coding RNA (lncRNA) AGAP2-AS1 acts as an oncogene in several types of cancers. However, the role and mechanism of AGAP2-AS1 in papillary thyroid carcinoma (PTC) remain unclear. Thus, in this study, we aimed to explore the role of AGAP2-AS1 in PTC. Our results showed that AGAP2-AS1 was significantly upregulated in PTC tissues. Knockdown of AGAP2-AS1 inhibited the proliferation, migration and invasion of PTC cells. In vivo experiment showed that AGAP2-AS1 knockdown inhibited the tumorigenesis of PTC. MiR-628-5p was found to act as a target miRNA of AGAP2-AS1 in PTC. The expression level of miR-628‐5p in PTC tissues was negatively associated with that of AGAP2-AS1. Inhibition of miR-628-5p attenuated the effects of AGAP2-AS1 knockdown on PTC. Moreover, miR-628-5p directly bound to the 3’UTR of KLF12 and inhibited the expression of KLF12. Knockdown of KLF12 enhanced the inhibitory effects of miR-628-5p on PTC cell proliferation and metastasis. In conclusion, these findings indicated that AGAP2-AS1 exerted an oncogenic role in PTC progression and metastasis. The effects of AGAP2-AS1 might be mediated by the regulation of miR-628-5p/KLF12 axis.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  • Abdullah MI, Junit SM, Ng KL, Jayapalan JJ, Karikalan B, Hashim OH (2019) Papillary thyroid cancer: genetic alterations and molecular biomarker investigations. Int J Med Sci 16(3):450–460

    Article  CAS  Google Scholar 

  • Bergmann JH, Spector DL (2014) Long non-coding RNAs: modulators of nuclear structure and function. Curr Opin Cell Biol 26(1):10–18

    Article  CAS  Google Scholar 

  • Bhan A, Soleimani M, Mandal SS (2017) Long noncoding RNA and cancer: a new paradigm. Cancer Res 77(15):3965–3981

    Article  CAS  Google Scholar 

  • Cabanillas ME, McFadden DG, Durante C (2016) Thyroid cancer. Lancet 388(10061):2783–2795

    Article  CAS  Google Scholar 

  • Chen J, Peng X, Dai Y (2019a) The long non-coding RNA (lncRNA) AGAP2-AS1 is upregulated in ovarian carcinoma and negatively regulates lncRNA MEG3. Med Sci Monit 25(1):4699–4704

    Article  CAS  Google Scholar 

  • Chen J, Hao P, Zheng T, Zhang Y (2019b) miR-628 reduces prostate cancer proliferation and invasion via the FGFR2 signaling pathway. Exp Ther Med 18(2):1005–1012

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ding S, Qu W, Jiao Y, Zhang J, Zhang C, Dang S (2018) LncRNA SNHG12 promotes the proliferation and metastasis of papillary thyroid carcinoma cells through regulating wnt/beta-catenin signaling pathway. Cancer Biomark 22(2):217–226

    Article  CAS  Google Scholar 

  • Ding L, Ding Y, Kong X, Wu J, Fu J, Yan G, Zhou H (2019) Dysregulation of Kruppel-like factor 12 in the development of endometrial cancer. Gynecol Oncol 152(1):177–184

    Article  CAS  Google Scholar 

  • Fatica A, Bozzoni, I (2014) Long non-coding RNAs: new players in cell differentiation and development. Nat Rev Genet 15(1):7–21

  • Feng J, Zhou Q, Yi H, Ma S, Li D, Xu Y, Wang J, Yin S (2019) A novel lncRNA n384546 promotes thyroid papillary cancer progression and metastasis by acting as a competing endogenous RNA of miR-145-5p to regulate AKT3. Cell Death Dis 10(6):433

    Article  Google Scholar 

  • Flintoft L (2013) Non-coding RNA: Structure and function for lncRNAs. Nat Rev Genet 14(9):598

    CAS  PubMed  Google Scholar 

  • Fu XM, Guo W, Li N, Liu HZ, Liu J, Qiu SQ, Zhang Q, Wang LC, Li F, Li CL (2017) The expression and function of long noncoding RNA lncRNA-ATB in papillary thyroid cancer. Eur Rev Med Pharmacol Sci 21(14):3239–3246

    PubMed  Google Scholar 

  • Godin-Heymann N, Brabetz S, Murillo MM, Saponaro M, Santos CR, Lobley A, East P, Chakravarty P, Matthews N, Kelly G, Jordan S, Castellano E, Downward J (2016) Tumour-suppression function of KLF12 through regulation of anoikis. Oncogene 35(25):3324–3334

    Article  CAS  Google Scholar 

  • Gur EO, Karaisli S, Haciyanli S, Kamer E, Genc H, Atahan K, Haciyanli M (2019) Multifocality related factors in papillary thyroid carcinoma. Asian J Surg 42(1):297–302

  • He Z, Yu L, Luo S, Li Q, Huang S, An Y (2019) RGS4 regulates proliferation and apoptosis of NSCLC cells via microRNA-16 and brain-derived neurotrophic factor. Onco Targets Ther 12(1):8701–8714

    Article  CAS  Google Scholar 

  • Kim SH, Park YY, Cho SN, Margalit O, Wang D, DuBois RN (2016) Kruppel-like factor 12 promotes colorectal cancer growth through early growth response protein 1. PLoS One 11(7):e0159899

    Article  Google Scholar 

  • Li M, Qian Z, Ma X, Lin X, You Y, Li Y, Chen T, Jiang H (2018) MiR-628-5p decreases the tumorigenicity of epithelial ovarian cancer cells by targeting at FGFR2. Biochem Biophys Res Commun 495(2):2085–2091

    Article  CAS  Google Scholar 

  • Li H, Han Q, Chen Y, Chen X, Ma R, Chang Q, Yin D (2019) Upregulation of the long non-coding RNA FOXD2-AS1 is correlated with tumor progression and metastasis in papillary thyroid cancer. Am J Transl Res 11(9):5457–5471

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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(1):238–247

    Article  Google Scholar 

  • Liu Z, Wang Y, Dou C, Sun L, Li Q, Wang L, Xu Q, Yang W, Liu Q, Tu K (2018) MicroRNA-1468 promotes tumor progression by activating PPAR-gamma-mediated AKT signaling in human hepatocellular carcinoma. J Exp Clin Cancer Res 37(1):49

    Article  Google Scholar 

  • Luo W, Li X, Song Z, Zhu X, Zhao S (2019) Long non-coding RNA AGAP2-AS1 exerts oncogenic properties in glioblastoma by epigenetically silencing TFPI2 through EZH2 and LSD1. Aging 11(11):3811–3823

    Article  CAS  Google Scholar 

  • Mercer TR, Dinger ME, Mattick JS (20090) Long non-coding RNAs: insights into functions. Nat Rev Genet 10(3):155–159

  • Qi X, Zhang DH, Wu N, Xiao JH, Wang X, Ma W (2015) ceRNA in cancer: possible functions and clinical implications. J Med Genet 52(10):710–718

    Article  Google Scholar 

  • Smillie CL, Sirey T, Ponting CP (2018) Complexities of post-transcriptional regulation and the modeling of ceRNA crosstalk. Crit Rev Biochem Mol Biol 53(3):231–245

    Article  CAS  Google Scholar 

  • Wang J, Liang C, Meng F, Xu X, Wu Y, Lu L (2019a) Lentivirus-mediated RNA interference targeting EBNA1 gene inhibits the growth of GT-38 cells in vitro and in vivo. Oncol Lett 18(3):2286–2291

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang M, Zhou L, Yu F, Zhang Y, Li P, Wang K (2019b) The functional roles of exosomal long non-coding RNAs in cancer. Cell Mol Life Sci 76(11):2059–2076

    Article  CAS  Google Scholar 

  • Wang JY, Lu SB, Wang JQ (2020) miR-628-5p promotes the growth and migration of osteosarcoma by targeting IFI44L. Biochem Cell Biol 98(2):99–105

    Article  CAS  Google Scholar 

  • Xie P, Wang Y, Liao Y, Han Q, Qiu Z, Chen Y, Zuo X (2019) MicroRNA-628-5p inhibits cell proliferation in glioma by targeting DDX59. J Cell Biochem 120(10):17293–17302

    Article  CAS  Google Scholar 

  • Yuan Q, Liu Y, Fan Y, Liu Z, Wang X, Jia M, Geng Z, Zhang J, Lu X (2018) LncRNA HOTTIP promotes papillary thyroid carcinoma cell proliferation, invasion and migration by regulating miR-637. Int J Biochem Cell Biol 98(1):1–9

    Article  CAS  Google Scholar 

  • Zhang Y, Xu Y, Feng L, Li F, Sun Z, Wu T, Shi X, Li J, Li X (2016) Comprehensive characterization of lncRNA-mRNA related ceRNA network across 12 major cancers. Oncotarget 7(39):64148–64167

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by the Hospital Fund of the First Affiliated Hospital of Xi’an Jiaotong University (No.2019ZYTS-04), Xi’an Science and Technology Project (No. 2019114613YX001SF04(5)), the Hospital Clinical Research Project of the First Affiliated Hospital of Xi’an Jiaotong University ( XJTU1AF-CRF-2020-014), The Special Reward Fund Project for Technological Transformation of Small and Medium-sized Enterprises in Shaanxi Province (2020, Xiaobao Yao), Key Research and Development Plan of Natural Science in Shaanxi Province (No. 2017SF-151), and the Basic Natural Science Research Program of Shaanxi Province (No. 2017JM8072).

Author information

Authors and Affiliations

Authors

Contributions

Zhiwei Zheng and Shaoqiang Zhang designed this manuscript. Chongwen Xu and Yuan Shao wrote this manuscript. Junsong Liu, Xiaobao Yao, Fang Quan, Qian Zhao, Ruimin Zhao performed experiments. Bo Kou, Honghui Li and Peng Han analyzed the data. Xuan Wang and Yanxia Bai revised the language of the manuscript; all the authors approved the manuscript for submission.

Corresponding authors

Correspondence to Zhiwei Zheng or Shaoqiang Zhang.

Ethics declarations

Conflict of interest

None.

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

Xu, C., Shao, Y., Liu, J. et al. Long non‐coding RNA AGAP2-AS1 promotes proliferation and metastasis in papillary thyroid cancer by miR-628-5p/KLF12 axis. J Bioenerg Biomembr 53, 235–245 (2021). https://doi.org/10.1007/s10863-021-09879-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10863-021-09879-3

Keywords

Navigation