Long Noncoding RNA FGFR3-AS1 Promotes Osteosarcoma Growth Through Regulating Its Natural Antisense Transcript FGFR3

Overview

Journal Mol Biol Rep

Specialty Molecular Biology

Date 2016 Mar 30

PMID 27022737

Citations 55

Authors

Jiabing Sun

Xuming Wang

Chunjiang Fu

Xiaoyu Wang

Jilong Zou

Hanbing Hua

Zhenggang Bi

Affiliations

Soon will be listed here.

Abstract

Long noncoding RNAs (lncRNAs), a new class of RNAs with no protein-coding potential, have been reported to have crucial roles in the regulation of a variety of tumors. However, the functions and molecular mechanisms of lncRNAs to osteosarcoma are still largely unknown. The purpose of this study is to examine the expression, functions and molecular mechanisms of a new lncRNA FGFR3 antisense transcript 1 (FGFR3-AS1) in osteosarcoma. The expression of FGFR3-AS1 was examined by real-time quantitative PCR. The regulation of FGFR3 by FGFR3-AS1 was examined by RNase protection assay, real-time quantitative PCR, western blotting, and luciferase reporter assay. The effects of FGFR3-AS1 on osteosarcoma cell proliferation and cell cycle were determined by Cell Counting Kit-8, Ethynyl deoxyuridine incorporation assay and flow cytometry. FGFR3-AS1 was upregulated in osteosarcoma. Increased FGFR3-AS1 expression correlates with large tumor size, advanced Enneking stage, metastasis and poor survival. Through antisense pairing with FGFR3 3'UTR, FGFR3-AS1 increases FGFR3 mRNA stability and upregulates FGFR3 expression. The expression of FGFR3-AS1 and FGFR3 is positively correlated in osteosarcoma tissues. Knockdown of FGFR3-AS1 inhibits the proliferation and cell cycle progression of osteosarcoma cells in vitro. Moreover, knockdown of FGFR3-AS1 inhibits xenograft tumor growth of osteosarcoma cells in vivo. These data demonstrate the mechanisms of how antisense noncoding RNA regulate the expression of sense genes, and show the pivotal functions of FGFR3-AS1 in osteosarcoma.

Citing Articles

LncRNAs as potential prognosis/diagnosis markers and factors driving drug resistance of osteosarcoma, a review.

Hu S, Han X, Liu G, Wang S Front Endocrinol (Lausanne). 2024; 15:1415722.

PMID: 39015175 PMC: 11249743. DOI: 10.3389/fendo.2024.1415722.

Emerging roles of long non-coding RNAs in osteosarcoma.

Liao X, Wei R, Zhou J, Wu K, Li J Front Mol Biosci. 2024; 11:1327459.

PMID: 38516191 PMC: 10955361. DOI: 10.3389/fmolb.2024.1327459.

Lncrna FGFR3-AS1 Is a Prognostic Indicator for Ovarian Cancer and Induces Cell Proliferation and Hinders Apoptosis.

Zhang Y, Sun L, Chen T, Yue Y, Zhao L, Zhang D Iran J Public Health. 2023; 52(11):2412-2416.

PMID: 38106830 PMC: 10719698. DOI: 10.18502/ijph.v52i11.14040.

Long intergenic non-coding RNA DIO3OS promotes osteosarcoma metastasis via activation of the TGF-β signaling pathway: a potential diagnostic and immunotherapeutic target for osteosarcoma.

Yuan J, Jia J, Wu T, Du Z, Chen Q, Zhang J Cancer Cell Int. 2023; 23(1):215.

PMID: 37752544 PMC: 10521498. DOI: 10.1186/s12935-023-03076-5.

Neat1 lncRNA organizes the inflammatory gene expressions in the dorsal root ganglion in neuropathic pain caused by nerve injury.

Maruyama M, Sakai A, Fukunaga T, Miyagawa Y, Okada T, Hamada M Front Immunol. 2023; 14:1185322.

PMID: 37614230 PMC: 10442554. DOI: 10.3389/fimmu.2023.1185322.

References

Sun Q, Liu H, Li L, Zhang S, Liu K, Liu Y . Long noncoding RNA-LET, which is repressed by EZH2, inhibits cell proliferation and induces apoptosis of nasopharyngeal carcinoma cell. Med Oncol. 2015; 32(9):226. DOI: 10.1007/s12032-015-0673-0. View

Kansara M, Teng M, Smyth M, Thomas D . Translational biology of osteosarcoma. Nat Rev Cancer. 2014; 14(11):722-35. DOI: 10.1038/nrc3838. View

Wang Y, Yao J, Meng H, Yu Z, Wang Z, Yuan X . A novel long non-coding RNA, hypoxia-inducible factor-2α promoter upstream transcript, functions as an inhibitor of osteosarcoma stem cells in vitro. Mol Med Rep. 2014; 11(4):2534-40. PMC: 4337490. DOI: 10.3892/mmr.2014.3024. View

Allison D, Carney S, Ahlmann E, Hendifar A, Chawla S, Fedenko A . A meta-analysis of osteosarcoma outcomes in the modern medical era. Sarcoma. 2012; 2012:704872. PMC: 3329715. DOI: 10.1155/2012/704872. View

Jaffe N, Puri A, Gelderblom H . Osteosarcoma: evolution of treatment paradigms. Sarcoma. 2013; 2013:203531. PMC: 3678494. DOI: 10.1155/2013/203531. View

Panzitt K, Tschernatsch M, Guelly C, Moustafa T, Stradner M, Strohmaier H . Characterization of HULC, a novel gene with striking up-regulation in hepatocellular carcinoma, as noncoding RNA. Gastroenterology. 2007; 132(1):330-42. DOI: 10.1053/j.gastro.2006.08.026. View

Faghihi M, Modarresi F, Khalil A, Wood D, Sahagan B, Morgan T . Expression of a noncoding RNA is elevated in Alzheimer's disease and drives rapid feed-forward regulation of beta-secretase. Nat Med. 2008; 14(7):723-30. PMC: 2826895. DOI: 10.1038/nm1784. View

Dong Y, Liang G, Yuan B, Yang C, Gao R, Zhou X . MALAT1 promotes the proliferation and metastasis of osteosarcoma cells by activating the PI3K/Akt pathway. Tumour Biol. 2014; 36(3):1477-86. DOI: 10.1007/s13277-014-2631-4. View

Mahmoudi S, Henriksson S, Corcoran M, Mendez-Vidal C, Wiman K, Farnebo M . Wrap53, a natural p53 antisense transcript required for p53 induction upon DNA damage. Mol Cell. 2009; 33(4):462-71. DOI: 10.1016/j.molcel.2009.01.028. View

10.

Yuan J, Yang F, Wang F, Ma J, Guo Y, Tao Q . A long noncoding RNA activated by TGF-β promotes the invasion-metastasis cascade in hepatocellular carcinoma. Cancer Cell. 2014; 25(5):666-81. DOI: 10.1016/j.ccr.2014.03.010. View

11.

Yin D, He X, Zhang E, Kong R, De W, Zhang Z . Long noncoding RNA GAS5 affects cell proliferation and predicts a poor prognosis in patients with colorectal cancer. Med Oncol. 2014; 31(11):253. DOI: 10.1007/s12032-014-0253-8. View

12.

Peng W, Gao W, Feng J . Long noncoding RNA HULC is a novel biomarker of poor prognosis in patients with pancreatic cancer. Med Oncol. 2014; 31(12):346. DOI: 10.1007/s12032-014-0346-4. View

13.

Lin X, Yang M, Xia T, Guo J . Increased expression of long noncoding RNA ABHD11-AS1 in gastric cancer and its clinical significance. Med Oncol. 2014; 31(7):42. DOI: 10.1007/s12032-014-0042-4. View

14.

Sadikovic B, Yoshimoto M, Chilton-MacNeill S, Thorner P, Squire J, Zielenska M . Identification of interactive networks of gene expression associated with osteosarcoma oncogenesis by integrated molecular profiling. Hum Mol Genet. 2009; 18(11):1962-75. DOI: 10.1093/hmg/ddp117. View

15.

Matsui K, Nishizawa M, Ozaki T, Kimura T, Hashimoto I, Yamada M . Natural antisense transcript stabilizes inducible nitric oxide synthase messenger RNA in rat hepatocytes. Hepatology. 2007; 47(2):686-97. DOI: 10.1002/hep.22036. View

16.

El-Naggar A, Veinotte C, Cheng H, Grunewald T, Negri G, Somasekharan S . Translational Activation of HIF1α by YB-1 Promotes Sarcoma Metastasis. Cancer Cell. 2015; 27(5):682-97. DOI: 10.1016/j.ccell.2015.04.003. View

17.

Klattenhoff C, Scheuermann J, Surface L, Bradley R, Fields P, Steinhauser M . Braveheart, a long noncoding RNA required for cardiovascular lineage commitment. Cell. 2013; 152(3):570-83. PMC: 3563769. DOI: 10.1016/j.cell.2013.01.003. View

18.

Yang M, Zhai X, Xia B, Wang Y, Lou G . Long noncoding RNA CCHE1 promotes cervical cancer cell proliferation via upregulating PCNA. Tumour Biol. 2015; 36(10):7615-22. DOI: 10.1007/s13277-015-3465-4. View

19.

McHugh C, Chen C, Chow A, Surka C, Tran C, McDonel P . The Xist lncRNA interacts directly with SHARP to silence transcription through HDAC3. Nature. 2015; 521(7551):232-6. PMC: 4516396. DOI: 10.1038/nature14443. View

20.

Li J, Liu L, Li J, Chen Y, Jiang X, Ouyang Y . Microarray expression profile of long noncoding RNAs in human osteosarcoma. Biochem Biophys Res Commun. 2013; 433(2):200-6. DOI: 10.1016/j.bbrc.2013.02.083. View