https://doi.org/10.4081/ejh.2021.3300
LncRNA FGD5-AS1 functions as an oncogene to upregulate GTPBP4 expression by sponging miR-873-5p in hepatocellular carcinoma
Submitted: 2 July 2021
Accepted: 11 October 2021
Published: 16 November 2021
Accepted: 11 October 2021
Abstract Views: 776
PDF: 441
HTML: 27
HTML: 27
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
The long non-coding FGD5-AS1 (LncFGD5-AS1) has been reported to be a novel carcinogenic gene and participant in regulating tumor progression by sponging microRNAs (miRNAs). However, the pattern of expression and the biological role of FGD5-AS1 in hepatocellular carcinoma (HCC) remains largely unknown. The expression level of FGD5-AS1 in tumor tissues and cell lines was measured by RT-qPCR. CCK-8, EdU, flow cytometry, wound healing, and transwell chamber assays were performed to investigate the role of FGD5-AS1 in cell proliferation, apoptosis, migration, and invasion in HCC. Dual luciferase reporter, and RNA pull-down assays were performed to identify the regulatory interactions among FGD5-AS1, miR-873-5p and GTP-binding protein 4 (GTPBP4). We found that the expression of FGD5-AS1 was upregulated in HCC tissues and cell lines. Moreover, the knockdown of FGD5-AS1 suppressed cell proliferation, migration and invasion, and induced apoptosis in HCC cells. Further studies demonstrated that FGD5-AS1 could function as a competitive RNA by sponging miR-873-5p in HCC cells. Moreover, GTPBP4 was identified as direct downstream target of miR-873-5p in HCC cells and FGD5-AS1mediated the effects of GTPBP4 by competitively binding with miR-873-5p. Taken together, this study demonstrated the regulatory role of FGD5-AS1 in the progression of HCC and identified the miR-873-5p/GTPBP4 axis as the direct downstream pathway. It represents a promising novel therapeutic strategy for HCC patients.
Donadon M, Solbiati L, Dawson A, Barry G, Sapisochin, G, Greig PD, et al. Hepatocellular carcinoma: The role of interventional oncology. Liver Cancer 2016;6:34-43.
DOI: https://doi.org/10.1159/000449346
Shen S, Lin Y, Yuan X, Shen L, Chen J, Chen L, et al. Biomarker MicroRNAs for diagnosis, prognosis and treatment of hepatocellular carcinoma: A functional survey and comparison. Sci Rep 2016;6:38311.
DOI: https://doi.org/10.1038/srep38311
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;71:209-49.
DOI: https://doi.org/10.3322/caac.21660
Llovet JM, Bustamante J, Castells A, Vilana R, Ayuso Mdel C, Sala M, et al. Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials. Hepatology 1999;29:62-7.
DOI: https://doi.org/10.1002/hep.510290145
Villanueva A. Hepatocellular carcinoma. N Engl J Med 2019;380:1450-62.
DOI: https://doi.org/10.1056/NEJMra1713263
Luo D, Deng B, Weng M, Luo Z, Nie X. A prognostic 4-lncRNA expression signature for lung squamous cell carcinoma. Artif Cells Nanomed Biotechnol 2018;46:1207-14.
DOI: https://doi.org/10.1080/21691401.2017.1366334
Renganathan A, Felley-Bosco E. Long noncoding RNAs in cancer and therapeutic potential. Adv Exp Med Biol 2017;1008:199-222.
DOI: https://doi.org/10.1007/978-981-10-5203-3_7
Yang G, Lu X, Yuan L. LncRNA: a link between RNA and cancer. Biochim Biophys Acta 2014;1839:1097-109.
DOI: https://doi.org/10.1016/j.bbagrm.2014.08.012
Sha QK, Chen L, Xi JZ, Song H. Long non-coding RNA LINC00858 promotes cells proliferation, migration and invasion by acting as a ceRNA of miR-22-3p in colorectal cancer. Artif Cells Nanomed Biotechnol 2019;47:1057-66.
DOI: https://doi.org/10.1080/21691401.2018.1544143
Liu YR, Tang RX, Huang WT, Ren FH, He RQ, Yang LH, et al. Long noncoding RNAs in hepatocellular carcinoma: Novel insights into their mechanism. World J Hepatol 2015;7:2781-91.
DOI: https://doi.org/10.4254/wjh.v7.i28.2781
Zeisel MB, Baumert TF. Translation and protein expression of lncRNAs: Impact for liver disease and hepatocellular carcinoma. Hepatology 2016;64:671-4.
DOI: https://doi.org/10.1002/hep.28653
Li G, Zhang H, Wan X, Yang X, Zhu C, Wang A, et al. Long noncoding RNA plays a key role in metastasis and prognosis of hepatocellular carcinoma. Biomed Res Int 2014;2014:780521.
DOI: https://doi.org/10.1155/2014/780521
Lin R, Maeda S, Liu C, Karin M, Edgington TS. A large noncoding RNA is a marker for murine hepatocellular carcinomas and a spectrum of human carcinomas. Oncogene 2007;26:851-8.
DOI: https://doi.org/10.1038/sj.onc.1209846
Lai MC, Yang Z, Zhou L, Zhu QQ, Xie HY, Zhang F, et al. Long non-coding RNA MALAT-1 overexpression predicts tumor recurrence of hepatocellular carcinoma after liver transplantation. Med Oncol 2012;29:1810-6.
DOI: https://doi.org/10.1007/s12032-011-0004-z
Yang F, Huo XS, Yuan SX, Zhang L, Zhou WP, Wang F, et al. Repression of the long noncoding RNA-LET by histone deacetylase 3 contributes to hypoxia-mediated metastasis. Mol Cell 2013;49:1083-96.
DOI: https://doi.org/10.1016/j.molcel.2013.01.010
Li D, Jiang X, Zhang X, Cao G, Wang D, Chen Z. Long noncoding RNA FGD5-AS1 promotes colorectal cancer cell proliferation, migration, and invasion through upregulating CDCA7 via sponging miR-302e. In Vitro Cell Dev Biol Anim 2019;55:577-85.
DOI: https://doi.org/10.1007/s11626-019-00376-x
Mendell JT. MicroRNAs: critical regulators of development, cellular physiology and malignancy. Cell Cycle 2005;4:1179-84.
DOI: https://doi.org/10.4161/cc.4.9.2032
Xie T, Pi G, Yang B, Ren H, Yu J, Ren Q, et al. Long non-coding RNA 520 is a negative prognostic biomarker and exhibits pro-oncogenic function in nasopharyngeal carcinoma carcinogenesis through regulation of miR-26b-3p/USP39 axis. Gene 2019;707:44-52.
DOI: https://doi.org/10.1016/j.gene.2019.02.093
Luo J, Zhu H, Jiang H, Cui Y, Wang M, Ni X, et al. The effects of aberrant expression of LncRNA DGCR5/miR-873-5p/TUSC3 in lung cancer cell progression. Cancer Med 2018;7:3331-41.
DOI: https://doi.org/10.1002/cam4.1566
Lu Z, Yu Y, Ding X, Jin D, Wang G, Zhou Y, et al. LncRNA FLJ33360 accelerates the metastasis in hepatocellular carcinoma by targeting miRNA-140/MMP9 axis. Am J Transl Res 2020;12:583-91.
Hongfeng Z, Andong J, Liwen S, Mingping B, Xiaowei Y, Mingyong L, et al. lncRNA RMRP knockdown suppress hepatocellular carcinoma biological activities via regulation miRNA-206/TACR1. J Cell Biochem 2020;121:1690-702.
DOI: https://doi.org/10.1002/jcb.29404
Liu WB, Jia WD, Ma JL, Xu GL, Zhou HC, Peng Y, et al. Knockdown of GTPBP4 inhibits cell growth and survival in human hepatocellular carcinoma and its prognostic significance. Oncotarget 2017;8:93984-97.
DOI: https://doi.org/10.18632/oncotarget.21500
Li L, Pang X, Zhu Z, Lu L, Yang J, Cao J, et al. GTPBP4 promotes gastric cancer progression via regulating P53 activity. Cell Physiol Biochem 2018;45:667-76.
DOI: https://doi.org/10.1159/000487160
Lu J, Mu X, Yin Q, Hu K. miR-106a contributes to prostate carcinoma progression through PTEN. Oncol Lett 2019;17:1327-32.
DOI: https://doi.org/10.3892/ol.2018.9697
Yin Q, Fischer L, Noethling C, Schaefer WR. In vitro-assessment of putative antiprogestin activities of phytochemicals and synthetic UV absorbers in human endometrial Ishikawa cells. Gynecol Endocrinol 2015;31:578-81.
DOI: https://doi.org/10.3109/09513590.2015.1047448
Fan Y, Li H, Yu Z, Dong W, Cui X, Ma J, et al. Long non-coding RNA FGD5-AS1 promotes non-small cell lung cancer cell proliferation through sponging hsa-miR-107 to up-regulate FGFRL1. Biosci Rep 2020;40:BSR20193309.
DOI: https://doi.org/10.1042/BSR20193309
Gao Y, Xie M, Guo Y, Yang Q, Hu S, Li Z. Long non-coding RNA FGD5-AS1 regulates cancer cell proliferation and chemoresistance in gastric cancer through miR-153-3p/CITED2 axis. Front Genet 2020;11:715.
DOI: https://doi.org/10.3389/fgene.2020.00715
Cao D, Yu T, Ou X. MiR-873-5P controls gastric cancer progression by targeting hedgehog-GLI signaling. Pharmazie 2016;71:603-6.
Wang L, Jiang F, Ma F, Zhang B. MiR-873-5p suppresses cell proliferation and epithelial-mesenchymal transition via directly targeting Jumonji domain-containing protein 8 through the NF-kappaB pathway in colorectal cancer. J Cell Commun Signal 2019;13:549-60.
DOI: https://doi.org/10.1007/s12079-019-00522-w
Zhu Y, Zhang X, Qi M, Zhang Y, Ding F. miR-873-5p inhibits the progression of colon cancer via repression of tumor suppressor candidate 3/AKT signaling. J Gastroenterol Hepatol 2019;34:2126-34.
DOI: https://doi.org/10.1111/jgh.14697
Zhu R, Guo W, Xu XJ, Zhu L. An integrating immune-related signature to improve prognosis of hepatocellular carcinoma. Comput Math Methods Med 2020;2020:8872329.
DOI: https://doi.org/10.1155/2020/8872329
Yu H, Jin S, Zhang N, Xu Q. Up-regulation of GTPBP4 in colorectal carcinoma is responsible for tumor metastasis. Biochem Biophys Res Commun 2016;480:48-54.
DOI: https://doi.org/10.1016/j.bbrc.2016.10.010
Supporting Agencies
the National Natural Science Foundation of ChinaHow to Cite
Zhang, N. ., Shen, H., Huang, S., Wang, F., Liu, H., Xie, F., … Chen, X. (2021). LncRNA FGD5-AS1 functions as an oncogene to upregulate GTPBP4 expression by sponging miR-873-5p in hepatocellular carcinoma . European Journal of Histochemistry, 65(4). https://doi.org/10.4081/ejh.2021.3300
Copyright (c) 2021 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Similar Articles
- S.A. Ferreira, J.L.A. Vasconcelos, R.C.W.C. Silva, C.L.B. Cavalcanti, C.L. Bezerra, M.J.B.M. Rêgo, E.I.C. Beltrão, Expression patterns of α2,3-Sialyltransferase I and α2,6-Sialyltransferase I in human cutaneous epithelial lesions , European Journal of Histochemistry: Vol. 57 No. 1 (2013)
- Bita Moudi, Zahra Heidari, Hamidreza Mahmoudzadeh-Sagheb, Seyed-Moayed Alavian, Kamran B. Lankarani, Parisa Farrokh, Jens Randel Nyengaard, Concomitant use of heat-shock protein 70, glutamine synthetase and glypican-3 is useful in diagnosis of HBV-related hepatocellular carcinoma with higher specificity and sensitivity , European Journal of Histochemistry: Vol. 62 No. 1 (2018)
- M. Artico, E. Bronzetti, V. Alicino, B. Ionta, S. Bosco, C. Grande, M. Bruno, F. M. Tranquilli Leali, G. Ionta, L. Fumagalli, Human gallbladder carcinoma: Role of neurotrophins, MIB-1, CD34 and CA15-3 , European Journal of Histochemistry: Vol. 54 No. 1 (2010)
- D. Fanni, M. Manchia, F. Lai, C. Gerosa, R. Ambu, G. Faa, Immunohistochemical markers of CYP3A4 and CYP3A7: a new tool towards personalized pharmacotherapy of hepatocellular carcinoma , European Journal of Histochemistry: Vol. 60 No. 2 (2016)
- Andreea Cioca, Amalia R. Ceausu, Irina Marin, Marius Raica, Anca M. Cimpean, The multifaceted role of podoplanin expression in hepatocellular carcinoma , European Journal of Histochemistry: Vol. 61 No. 1 (2017)
- Yan Wang, Jie Sun, Ninghua Yao, Correlation of the AKT/mTOR signaling pathway with the clinicopathological features and prognosis of nasopharyngeal carcinoma , European Journal of Histochemistry: Vol. 65 No. 4 (2021)
- Z. Protrka, S. Arsenijevic, A. Dimitrijevic, S. Mitrovic, V. Stankovic, M. Milosavljevic, T. Kastratovic, J. Djuric, Co-overexpression of bcl-2 and c-myc in uterine cervix carcinomas and premalignant lesions , European Journal of Histochemistry: Vol. 55 No. 1 (2011)
- Zhiyang Wang, Jing Li, Ziwei Liu, Ling Yue, Nrf2 as a novel diagnostic biomarker for papillary thyroid carcinoma , European Journal of Histochemistry: Vol. 67 No. 2 (2023)
- S. Soddu, E. Di Felice, S. Cabras, M.E. Castellanos, L. Atzori, G. Faa, L. Pilloni, IMP-3 expression in keratoacanthomas and squamous cell carcinomas of the skin: an immunohistochemical study , European Journal of Histochemistry: Vol. 57 No. 1 (2013)
- C. Cui, P. Lal, S. Master, Y. Ma, T. Baradet, Z. Bing, Expression of parafibromin in major renal cell tumors , European Journal of Histochemistry: Vol. 56 No. 4 (2012)
You may also start an advanced similarity search for this article.
