LncRNA FBXO18-AS promotes gastric cancer progression by TGF-β1/Smad signaling

Submitted: 2 February 2023
Accepted: 9 June 2023
Published: 20 June 2023
Abstract Views: 498
PDF: 346
Supplementary: 39
HTML: 11
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.


For the digestive system, there exists one common malignant tumor, known as gastric cancer. It is the third most prevalent type of tumor among different tumors worldwide. It has been reported that long noncoding RNAs (lncRNAs), participate in various biological processes of gastric cancer. However, there are still many lncRNAs with unknown functions, and we discovered a novel lncRNA designated as FBXO18-AS. Whether lncRNAFBXO18-AS participates in gastric cancer progression is still unknown. Bioinformatic analysis, immunohistochemistry, Western blotting, and qPCR were carried out to explore FBXO18-AS and TGF-β1 expression. In addition, EdU, MTS, migration and transwell assays were performed to investigate the invasion, proliferation and migration of gastric cancer in vitro. We first discovered that FBXO18-AS expression was upregulated in gastric cancer and linked to poorer outcomes among patients with gastric cancer. Then, we confirmed that FBXO18-AS promoted the proliferation, invasion, migration, and an EMT-like process in gastric cancer in vivo and in vitro. Mechanistically, FBXO18-AS was found to be involved in the progression of gastric cancer by modulating TGF-β1/Smad signaling. Therefore, it might offer a possible biomarker for gastric cancer diagnosis and an effective strategy for clinical treatment.



PlumX Metrics


Download data is not yet available.


Smyth EC, Nilsson M, Grabsch HI, Van Grieken NCT, Lordick F. Gastric cancer. Lancet 2020;396:635-48. DOI: https://doi.org/10.1016/S0140-6736(20)31288-5
Song Z, Wu Y, Yang J, Yang D, Fang X. Progress in the treatment of advanced gastric cancer. Tumour Biol 2017 39:1010428317714626. DOI: https://doi.org/10.1177/1010428317714626
Feng W, Ding Y, Zong W, Ju S. Non-coding RNAs in regulating gastric cancer metastasis. Clin Chim Acta 2019;496:125-33. DOI: https://doi.org/10.1016/j.cca.2019.07.003
Peng Z, Wang CX, Fang EH, Wang G B, Tong Q. Role of epithelial-mesenchymal transition in gastric cancer initiation and progression. World J Gastroenterol 2014;20:5403-10. DOI: https://doi.org/10.3748/wjg.v20.i18.5403
Wei L, Sun J, Zhang N, Zheng Y, Wang X, Lv L, et al. Noncoding RNAs in gastric cancer: implications for drug resistance. Mol Cancer 2020;19:62. DOI: https://doi.org/10.1186/s12943-020-01185-7
Zhang XQ, Leung G K. Long non-coding RNAs in glioma: functional roles and clinical perspectives. Neurochem Int 2014;77:78-85. DOI: https://doi.org/10.1016/j.neuint.2014.05.008
Chen M, Wu X, Ma W, Zhou Q, Wang X, Zhang R, et al. Decreased expression of lncRNA VPS9D1-AS1 in gastric cancer and its clinical significance. Cancer Biomark 2017;21:23-8. DOI: https://doi.org/10.3233/CBM-170172
Cech T R, Steitz J A. The noncoding RNA revolution-trashing old rules to forge new ones. Cell 2014;157:77-94. DOI: https://doi.org/10.1016/j.cell.2014.03.008
Zhang F, Li Y, Xu W, He L, Tan Y, Xu H. Long non-coding RNA ZFAS1 regulates the malignant progression of gastric cancer via the microRNA-200b-3p/Wnt1 axis. Biosci Biotechnol Biochem 2019;83:1289-99. DOI: https://doi.org/10.1080/09168451.2019.1606697
Ghafouri-Fard S, Taheri M. Long non-coding RNA signature in gastric cancer. Exp Mol Pathol 2020;113:104365. DOI: https://doi.org/10.1016/j.yexmp.2019.104365
Chen S, Jundi D, Wang W, Ren C. LINC01857 promotes the proliferation, migration, and invasion of gastric cancer cells via regulating miR-4731-5p/HOXC6. Can J Physiol Pharmacol 2022;100:689-701. DOI: https://doi.org/10.1139/cjpp-2021-0411
Zhang P, Chen C, Zhang J, Yu X. LncRNA CRYM-AS1 inhibits gastric cancer progression via epigenetically regulating CRYM. Ann Clin Lab Sci 2022;52:249-59. DOI: https://doi.org/10.21203/rs.3.rs-593172/v1
Jiang Y, Zhou J, Hou D, Luo P, Gao H, Ma Y, et al. Prosaposin is a biomarker of mesenchymal glioblastoma and regulates mesenchymal transition through the TGF-β1/Smad signaling pathway. J Pathol 2019;249:26-38. DOI: https://doi.org/10.1002/path.5278
Guo Z, Li G, Bian E, Ma CC, Wan J, Zhao B. TGF-β-mediated repression of MST1 by DNMT1 promotes glioma malignancy. Biomed Pharmacother 2017;94:774-80. DOI: https://doi.org/10.1016/j.biopha.2017.07.081
Jiang Y, Zhou J, Zhao J, Hou D, Zhang H, Li L, et al. MiR-18a-downregulated RORA inhibits the proliferation and tumorigenesis of glioma using the TNF-alpha-mediated NF-kappaB signaling pathway. EBioMedicine 2020;52:102651. DOI: https://doi.org/10.1016/j.ebiom.2020.102651
Jiang Y, Han S, Cheng W, Wang Z, Wu A. NFAT1-regulated IL6 signalling contributes to aggressive phenotypes of glioma. Cell Commun Signal 2017;15 54. DOI: https://doi.org/10.1186/s12964-017-0210-1
Jiang Y, Zhou J, Luo P, Gao H, Ma Y, Chen YS, et al. Prosaposin promotes the proliferation and tumorigenesis of glioma through toll-like receptor 4 (TLR4)-mediated NF-kappaB signaling pathway. EBioMedicine 2018;37:78-90. DOI: https://doi.org/10.1016/j.ebiom.2018.10.053
Torre L A, Bray F, Siegel R L, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015;65:87-108. DOI: https://doi.org/10.3322/caac.21262
Chen H, Guan R, Lei Y, Chen J, Ge Q, Zhang X, et al. Lymphangiogenesis in gastric cancer regulated through Akt/mTOR-VEGF-C/VEGF-D axis. BMC Cancer 2015;15:103. DOI: https://doi.org/10.1186/s12885-015-1109-0
Qi X, Zhang DH, Wu N, Xiao JH, Wang X, Ma W. ceRNA in cancer: possible functions and clinical implications. J Med Genet 2015;52:710-8. DOI: https://doi.org/10.1136/jmedgenet-2015-103334
Li Z, Lü M, Zhou Y, Xu L, Jiang Y, Liu Y, et al. Role of long non-coding RNAs in the chemoresistance of gastric cancer: a systematic review. Onco Targets Ther 2021;14:503-18. DOI: https://doi.org/10.2147/OTT.S294378
Ye Y, Yang S, Han Y, Sun J, Xv L, Wu L, et al. HOXD-AS1 confers cisplatin resistance in gastric cancer through epigenetically silencing PDCD4 via recruiting EZH2. Open Biol 2019;9:190068. DOI: https://doi.org/10.1098/rsob.190068
Guo Y, Yue P, Wang Y, Chen G, Li Y. PCAT-1 contributes to cisplatin resistance in gastric cancer through miR-128/ZEB1 axis. Biomed Pharmacother 2019;118:109255. DOI: https://doi.org/10.1016/j.biopha.2019.109255
Wu Q, Ma J, Wei J, Meng W, Wang Y, Shi M. FOXD1-AS1 regulates FOXD1 translation and promotes gastric cancer progression and chemoresistance by activating the PI3K/AKT/mTOR pathway. Mol Oncol 2021;15:299-316. DOI: https://doi.org/10.1002/1878-0261.12728
Tian X, Zhu X, Yan T, Yu C, Shen C, Hong J, et al. Differentially expressed lncRNAs in gastric cancer patients: a potential biomarker for gastric cancer prognosis. J Cancer 2017;8:2575-86. DOI: https://doi.org/10.7150/jca.19980
Yiren H, Yingcong Y, Sunwu Y, Keqin L, Xiaochun T, Senrui C, et al. Long noncoding RNA MALAT1 regulates autophagy associated chemoresistance via miR-23b-3p sequestration in gastric cancer. Mol Cancer 2017;16:174. DOI: https://doi.org/10.1186/s12943-017-0743-3
Xu W, He L, Li Y, Tan Y, Zhang F, Xu H. Silencing of lncRNA ZFAS1 inhibits malignancies by blocking Wnt/β-catenin signaling in gastric cancer cells. Biosci Biotechnol Biochem 2018;82:456-65. DOI: https://doi.org/10.1080/09168451.2018.1431518
Zhou Y, Zhang Q, Liao B, Qiu X, Hu S, Xu Q. circ_0006089 promotes gastric cancer growth, metastasis, glycolysis, and angiogenesis by regulating miR-361-3p/TGFB1. Cancer Sci 2022;113:2044-55. DOI: https://doi.org/10.1111/cas.15351
Hu YZ, Hu ZL, Liao TY, Li Y, Pan YL. LncRNA SND1-IT1 facilitates TGF-β1-induced epithelial-to-mesenchymal transition via miR-124/COL4A1 axis in gastric cancer. Cell Death Discov 2022;8:73. DOI: https://doi.org/10.1038/s41420-021-00793-6

Ethics Approval

The study on human clinical specimens was approved and authorized by the Ethics Committee of Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine (protocol no. 2022-K067). Written informed consent was obtained from all enrolled patients, The Animal Care Committee of Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine approved the experiments on animals (protocol no. xmsq2022-0667)

Supporting Agencies

Public Welfare Technology Research Plan / Social Development Project of Zhejiang, China., Wenzhou Basic Science Research Project.

How to Cite

Zhang, Y., Zheng, W., Zhang, L., Gu, Y., Zhu, L., & Huang, Y. (2023). LncRNA FBXO18-AS promotes gastric cancer progression by TGF-β1/Smad signaling. European Journal of Histochemistry, 67(2). https://doi.org/10.4081/ejh.2023.3667