Home Life Sciences Long non-coding RNA FAM66C regulates glioma growth via the miRNA/LATS1 signaling pathway
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Long non-coding RNA FAM66C regulates glioma growth via the miRNA/LATS1 signaling pathway

  • Kai Xiao and Gang Peng EMAIL logo
Published/Copyright: December 22, 2021
Biological Chemistry
From the journal Biological Chemistry Volume 403 Issue 7

Abstract

Glioma is one of the most common primary intracranial carcinomas and typically associated with a dismal prognosis and poor quality of life. The identification of novel oncogenes is clinically valuable for early screening and prevention. Recently, the studies have revealed that long non-coding RNAs (lncRNAs) play important roles in the development and progression of cancers including glioma. The expression of lncRNA FAM66C is reduced in glioma cell lines and clinical samples compared to non-tumor samples. Knockdown of FAM66C in U87 and U251 cells significantly promoted cell proliferation and migration, respectively. Furthermore, the correlation between FAM66C and Hippo pathway regulators YAP1 and LATS1, along with the alteration of their protein expression level indicated that FAM66C regulated cell growth through this pathway. Moreover, luciferase assay demonstrated that another two noncoding RNAs, miR15a/miR15b, directly bonded to the 3′UTR of LATS1 to facilitated its transcriptional expression and inhibited cell growth. In addition, the luciferase activity of FAM66C was block by miR15a/miR15b, and the promotion of cell growth effects caused by FAM66C deficiency was attenuated by miR15a/miR15b mimics, further proved that FAM66C functioned as a competing endogenous RNA to regulate glioma growth via the miRNA/LATS1 signaling pathway.

Keywords: glioma; LATS1; lncRNA; miRNA; tumor progression
Corresponding author: Gang Peng, Department of Neurosurgery, Xiangya Hospital of Central South University, Xiangya Road, Kaifu District, Changsha 410008, Hunan Province, People’s Republic of China, E-mail:

Funding source: National Key Technology Research and Development Program of the Ministry of Science and Technology of China

Award Identifier / Grant number: 2014BAI04B01 2014BAI04B02 2015BAI12B04

Funding source: National Natural Science Foundation of China http://dx.doi.org/10.13039/501100001809

Award Identifier / Grant number: No. 81801908

Acknowledgments

We thank the Editors for constructive comments on the manuscript.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This work was funded by grants from the National Natural Science Foundation of China (No. 81801908) and the National Key Technology Research and Development Program of the Ministry of Science and Technology of China (Nos. 2014BAI04B01, 2014BAI04B02 and 2015BAI12B04).

  3. Conflict of interest statement: The author reports no conflicts of interest in this work.

  4. Ethics approval and informed consent: About human tissues, the experimental use of surgical samples in this manuscript have been performed in accordance with the principles stated in the Declaration of Helsinki, also are approved by patients and Xiangya Hospital Ethics Committee. The approval number is 2021-XMSB-0102. All patients were provided informed consent, and signed up voluntarily.

  5. Consent for publication: Written informed consent for publication was obtained from all participants.

  6. Data availability: The data of the current study are available from the corresponding author on reasonable request. The GBMLGG RNA sequencing (RNAseq) data was downloaded from GlioVis (http://gliovis.bioinfo.cnio.es/).

References

Aldape, K., Zadeh, G., Mansouri, S., Reifenberger, G., and von Deimling, A. (2015). Glioblastoma: pathology, molecular mechanisms and markers. Acta Neuropathol. 129: 829–848. https://doi.org/10.1007/s00401-015-1432-1.Search in Google Scholar PubMed

Almeida, M., Pintacuda, G., Masui, O., Koseki, Y., Gdula, M., Cerase, A., Brown, D., Mould, A., Innocent, C., Nakayama, M., et al.. (2017). PCGF3/5-PRC1 initiates Polycomb recruitment in X chromosome inactivation. Science 356: 1081–1084. https://doi.org/10.1126/science.aal2512.Search in Google Scholar PubMed PubMed Central

Baspinar, Y., Elmaci, I., Ozpinar, A., and Altinoz, M.A. (2020). Long non-coding RNA MALAT1 as a key target in pathogenesis of glioblastoma. Janus faces or Achilles’ heal? Gene 739: 144518. https://doi.org/10.1016/j.gene.2020.144518.Search in Google Scholar PubMed

Bian, E.B., Ma, C.C., He, X.J., Wang, C., Zong, G., Wang, H.L., and Zhao, B. (2016). Epigenetic modification of miR-141 regulates SKA2 by an endogenous ‘sponge’ HOTAIR in glioma. Oncotarget 7: 30610–30625. https://doi.org/10.18632/oncotarget.8895.Search in Google Scholar PubMed PubMed Central

Buonfiglioli, A., Efe, I.E., Guneykaya, D., Ivanov, A., Huang, Y., Orlowski, E., Kruger, C., Deisz, R.A., Markovic, D., Fluh, C., et al.. (2019). let-7 microRNAs regulate microglial function and suppress glioma growth through toll-like receptor 7. Cell Rep. 29: 3460–3471.e7. https://doi.org/10.1016/j.celrep.2019.11.029.Search in Google Scholar PubMed

Bush, N.A., Chang, S.M., and Berger, M.S. (2017). Current and future strategies for treatment of glioma. Neurosurg. Rev. 40: 1–14. https://doi.org/10.1007/s10143-016-0709-8.Search in Google Scholar PubMed

Campos-Parra, A.D., Mitznahuatl, G.C., Pedroza-Torres, A., Romo, R.V., Reyes, F.I.P., Lopez-Urrutia, E., and Perez-Plasencia, C. (2017). Micro-RNAs as potential predictors of response to breast cancer systemic therapy: future clinical implications. Int. J. Mol. Sci. 18: 1182. https://doi.org/10.3390/ijms18061182.Search in Google Scholar PubMed PubMed Central

Chesi, M., Stein, C.K., Garbitt, V.M., Sharik, M.E., Asmann, Y.W., Bergsagel, M., Riggs, D.L., Welsh, S.J., Meermeier, E.W., Kumar, S.K., et al.. (2020). Monosomic loss of MIR15A/MIR16-1 is a driver of multiple myeloma proliferation and disease progression. Blood Cancer Discov. 1: 68–81. https://doi.org/10.1158/0008-5472.bcd-19-0068.Search in Google Scholar

Esteller, M. (2011). Non-coding RNAs in human disease. Nat. Rev. Genet. 12: 861–874. https://doi.org/10.1038/nrg3074.Search in Google Scholar PubMed

Fatica, A. and Bozzoni, I. (2014). Long non-coding RNAs: new players in cell differentiation and development. Nat. Rev. Genet. 15: 7–21. https://doi.org/10.1038/nrg3606.Search in Google Scholar PubMed

Fu, Z., Luo, W., Wang, J., Peng, T., Sun, G., Shi, J., Li, Z., and Zhang, B. (2017). Malat1 activates autophagy and promotes cell proliferation by sponging miR-101 and upregulating STMN1, RAB5A and ATG4D expression in glioma. Biochem. Biophys. Res. Commun. 492: 480–486. https://doi.org/10.1016/j.bbrc.2017.08.070.Search in Google Scholar PubMed

Gu, J., Lu, Z., Ji, C., Chen, Y., Liu, Y., Lei, Z., Wang, L., Zhang, H.T., and Li, X. (2017). Melatonin inhibits proliferation and invasion via repression of miRNA-155 in glioma cells. Biomed. Pharmacother. 93: 969–975. https://doi.org/10.1016/j.biopha.2017.07.010.Search in Google Scholar PubMed

Hakar, M.H. and Wood, M.D. (2020). Updates in pediatric glioma pathology. Surg Pathol Clin 13: 801–816. https://doi.org/10.1016/j.path.2020.08.006.Search in Google Scholar PubMed

He, L. and Hannon, G.J. (2004). MicroRNAs: small RNAs with a big role in gene regulation. Nat. Rev. Genet. 5: 522–531. https://doi.org/10.1038/nrg1379.Search in Google Scholar PubMed

Jiang, X.H. and Liu, Y.Y. (2020). LINC00467 promotes proliferation and invasion in glioma via interacting with miRNA-485-5p. Eur. Rev. Med. Pharmacol. Sci. 24: 766–772. https://doi.org/10.26355/eurrev_202001_20057.Search in Google Scholar PubMed

Johnson, R. and Halder, G. (2014). The two faces of Hippo: targeting the Hippo pathway for regenerative medicine and cancer treatment. Nat. Rev. Drug Discov. 13: 63–79. https://doi.org/10.1038/nrd4161.Search in Google Scholar PubMed PubMed Central

Justice, R.W., Zilian, O., Woods, D.F., Noll, M., and Bryant, P.J. (1995). The Drosophila tumor suppressor gene warts encodes a homolog of human myotonic dystrophy kinase and is required for the control of cell shape and proliferation. Genes Dev. 9: 534–546. https://doi.org/10.1101/gad.9.5.534.Search in Google Scholar PubMed

Komori, T. (2017). The 2016 WHO classification of tumours of the central nervous system: the major points of revision. Neurol. Med. Chir. (Tokyo) 57: 301–311. https://doi.org/10.2176/nmc.ra.2017-0010.Search in Google Scholar PubMed PubMed Central

Liu-Chittenden, Y., Huang, B., Shim, J.S., Chen, Q., Lee, S.J., Anders, R.A., Liu, J.O., and Pan, D. (2012). Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP. Genes Dev. 26: 1300–1305. https://doi.org/10.1101/gad.192856.112.Search in Google Scholar PubMed PubMed Central

Louis, D.N., Perry, A., Reifenberger, G., von Deimling, A., Figarella-Branger, D., Cavenee, W.K., Ohgaki, H., Wiestler, O.D., Kleihues, P., and Ellison, D.W. (2016). The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 131: 803–820. https://doi.org/10.1007/s00401-016-1545-1.Search in Google Scholar PubMed

Malta, T.M., de Souza, C.F., Sabedot, T.S., Silva, T.C., Mosella, M.S., Kalkanis, S.N., Snyder, J., Castro, A.V.B., and Noushmehr, H. (2018). Glioma CpG island methylator phenotype (G-CIMP): biological and clinical implications. Neuro Oncol. 20: 608–620. https://doi.org/10.1093/neuonc/nox183.Search in Google Scholar PubMed PubMed Central

Mendell, J.T. (2005). MicroRNAs: critical regulators of development, cellular physiology and malignancy. Cell Cycle 4: 1179–1184. https://doi.org/10.4161/cc.4.9.2032.Search in Google Scholar PubMed

Moroishi, T., Hansen, C.G., and Guan, K.L. (2015). The emerging roles of YAP and TAZ in cancer. Nat. Rev. Cancer 15: 73–79. https://doi.org/10.1038/nrc3876.Search in Google Scholar PubMed PubMed Central

Mrugala, M.M. (2013). Advances and challenges in the treatment of glioblastoma: a clinician’s perspective. Discov. Med. 15: 221–230.Search in Google Scholar

Musumeci, M., Coppola, V., Addario, A., Patrizii, M., Maugeri-Sacca, M., Memeo, L., Colarossi, C., Francescangeli, F., Biffoni, M., Collura, D., et al.. (2011). Control of tumor and microenvironment cross-talk by miR-15a and miR-16 in prostate cancer. Oncogene 30: 4231–4242. https://doi.org/10.1038/onc.2011.140.Search in Google Scholar PubMed

Omuro, A. and DeAngelis, L.M. (2013). Glioblastoma and other malignant gliomas: a clinical review. JAMA 310: 1842–1850. https://doi.org/10.1001/jama.2013.280319.Search in Google Scholar PubMed

Park, J.A. and Kwon, Y.G. (2018). Hippo-YAP/TAZ signaling in angiogenesis. BMB Rep 51: 157–162. https://doi.org/10.5483/bmbrep.2018.51.3.016.Search in Google Scholar PubMed PubMed Central

Peng, G., Liao, Y., and Shen, C. (2017a). miRNA-429 inhibits astrocytoma proliferation and invasion by targeting BMI1. Pathol. Oncol. Res. 23: 369–376. https://doi.org/10.1007/s12253-016-0113-2.Search in Google Scholar PubMed

Peng, W.X., Koirala, P., and Mo, Y.Y. (2017b). LncRNA-mediated regulation of cell signaling in cancer. Oncogene 36: 5661–5667. https://doi.org/10.1038/onc.2017.184.Search in Google Scholar PubMed PubMed Central

Peng, Z., Liu, C., and 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.Search in Google Scholar PubMed PubMed Central

Ricieri Brito, J.A., Gomes, C.C., Santos Pimenta, F.J., Barbosa, A.A., Prado, M.A., Prado, V.F., Gomez, M.V., and Gomez, R.S. (2010). Reduced expression of mir15a in the blood of patients with oral squamous cell carcinoma is associated with tumor staging. Exp. Ther. Med. 1: 217–221. https://doi.org/10.3892/etm_00000035.Search in Google Scholar PubMed PubMed Central

Rinn, J.L. and Chang, H.Y. (2012). Genome regulation by long noncoding RNAs. Annu. Rev. Biochem. 81: 145–166. https://doi.org/10.1146/annurev-biochem-051410-092902.Search in Google Scholar PubMed PubMed Central

Seo, Y.E., Suh, H.W., Bahal, R., Josowitz, A., Zhang, J., Song, E., Cui, J., Noorbakhsh, S., Jackson, C., Bu, T., et al.. (2019). Nanoparticle-mediated intratumoral inhibition of miR-21 for improved survival in glioblastoma. Biomaterials 201: 87–98. https://doi.org/10.1016/j.biomaterials.2019.02.016.Search in Google Scholar PubMed PubMed Central

Shibata, M., Ham, K., and Hoque, M.O. (2018). A time for YAP1: tumorigenesis, immunosuppression and targeted therapy. Int. J. Cancer 143: 2133–2144. https://doi.org/10.1002/ijc.31561.Search in Google Scholar PubMed PubMed Central

Stupp, R., Mason, W.P., van den Bent, M.J., Weller, M., Fisher, B., Taphoorn, M.J., Belanger, K., Brandes, A.A., Marosi, C., Bogdahn, U., et al.. (2005). Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med. 352: 987–996. https://doi.org/10.1056/nejmoa043330.Search in Google Scholar

Tian, W., Wu, W., Li, X., Rui, X., and Wu, Y. (2019). MiRNA-139-3p inhibits the proliferation, invasion, and migration of human glioma cells by targeting MDA-9/syntenin. Biochem. Biophys. Res. Commun. 508: 295–301. https://doi.org/10.1016/j.bbrc.2018.11.144.Search in Google Scholar PubMed

Trojan, L.A., Kopinski, P., Mazurek, A., Chyczewski, L., Ly, A., Jarocki, P., Niklinski, J., Shevelev, A., Trzos, R., Pan, Y., et al.. (2003). IGF-I triple helix gene therapy of rat and human gliomas. Rocz Akad Med Bialymst 48: 18–27.Search in Google Scholar

Ulitsky, I. and Bartel, D.P. (2013). lincRNAs: genomics, evolution, and mechanisms. Cell 154: 26–46. https://doi.org/10.1016/j.cell.2013.06.020.Search in Google Scholar PubMed PubMed Central

van Bakel, H., Nislow, C., Blencowe, B.J., and Hughes, T.R. (2010). Most “dark matter” transcripts are associated with known genes. PLoS Biol. 8: e1000371. https://doi.org/10.1371/journal.pbio.1000371.Search in Google Scholar PubMed PubMed Central

Vishnoi, A. and Rani, S. (2017). MiRNA biogenesis and regulation of diseases: an overview. Methods Mol. Biol. 1509: 1–10. https://doi.org/10.1007/978-1-4939-6524-3_1.Search in Google Scholar PubMed

Wang, L., Ma, J., Wang, X., Peng, F., Chen, X., Zheng, B., Wang, C., Dai, Z., Ai, J., and Zhao, S. (2018). Kaiso (ZBTB33) downregulation by miRNA 181a inhibits cell proliferation, invasion, and the epithelial-mesenchymal transition in glioma cells. Cell. Physiol. Biochem. 48: 947–958. https://doi.org/10.1159/000491963.Search in Google Scholar PubMed

Wang, Y., Chen, L., Chen, B., Li, X., Kang, J., Fan, K., Hu, Y., Xu, J., Yi, L., Yang, J., et al.. (2013). Mammalian ncRNA-disease repository: a global view of ncRNA-mediated disease network. Cell Death Dis. 4: e765. https://doi.org/10.1038/cddis.2013.292.Search in Google Scholar PubMed PubMed Central

Watson, K.L. (1995). Drosophila warts–tumor suppressor and member of the myotonic dystrophy protein kinase family. Bioessays 17: 673–676. https://doi.org/10.1002/bies.950170803.Search in Google Scholar PubMed

Xie, T., Liu, P., Chen, L., Chen, Z., Luo, Y., Chen, X., Feng, Y., and Luo, X. (2015). MicroRNA-15a down-regulation is associated with adverse prognosis in human glioma. Clin. Transl. Oncol. 17: 504–510. https://doi.org/10.1007/s12094-014-1265-8.Search in Google Scholar PubMed

Xie, Y., Gu, J., Qin, Z., Ren, Z., Wang, Y., Shi, H., and Chen, B. (2020). Long non-coding RNA FAM66C is associated with clinical progression and promotes cell proliferation by inhibiting proteasome pathway in prostate cancer. Cell Biochem. Funct. 38: 1006–1016. https://doi.org/10.1002/cbf.3531.Search in Google Scholar PubMed

Xin, X., Wu, M., Meng, Q., Wang, C., Lu, Y., Yang, Y., Li, X., Zheng, Q., Pu, H., Gui, X., et al.. (2018). Long noncoding RNA HULC accelerates liver cancer by inhibiting PTEN via autophagy cooperation to miR15a. Mol. Cancer 17: 94. https://doi.org/10.1186/s12943-018-0843-8.Search in Google Scholar PubMed PubMed Central

Zhang, X.Q., Kiang, K.M., Wang, Y.C., Pu, J.K., Ho, A., Cheng, S.Y., Lee, D., Zhang, P.D., Chen, J.J., Lui, W.M., et al.. (2015). IDH1 mutation-associated long non-coding RNA expression profile changes in glioma. J. Neuro Oncol. 125: 253–263. https://doi.org/10.1007/s11060-015-1916-9.Search in Google Scholar PubMed

Zhang, X.Q., Sun, S., Lam, K.F., Kiang, K.M., Pu, J.K., Ho, A.S., Lui, W.M., Fung, C.F., Wong, T.S., and Leung, G.K. (2013). A long non-coding RNA signature in glioblastoma multiforme predicts survival. Neurobiol. Dis. 58: 123–131. https://doi.org/10.1016/j.nbd.2013.05.011.Search in Google Scholar PubMed

Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/hsz-2021-0333).

Received: 2021-07-27
Accepted: 2021-12-07
Published Online: 2021-12-22
Published in Print: 2022-06-27

© 2021 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

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  2. Review
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  5. Protein Structure and Function
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https://doi.org/10.1515/hsz-2021-0333
Keywords for this article
glioma; LATS1; lncRNA; miRNA; tumor progression

Articles in the same Issue

  1. Frontmatter
  2. Review
  3. Chemerin – exploring a versatile adipokine
  4. Research Articles/Short Communications
  5. Protein Structure and Function
  6. Evolutionary adaptation of DHFR via expression of enzyme isoforms with various binding properties and dynamics behavior: a bioinformatics and computational study
  7. Cell Biology and Signaling
  8. SRPK1 promotes cell proliferation and tumor growth of osteosarcoma through activation of the NF-κB signaling pathway
  9. LINC00520 up-regulates SOX5 to promote cell proliferation and invasion by miR-4516 in human hepatocellular carcinoma
  10. Long non-coding RNA FAM66C regulates glioma growth via the miRNA/LATS1 signaling pathway
  11. CERKL alleviates ischemia reperfusion-induced nervous system injury through modulating the SIRT1/PINK1/Parkin pathway and mitophagy induction
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