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2000
Volume 17, Issue 1
  • ISSN: 1874-4672
  • E-ISSN: 1874-4702
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Abstract

Background

Increasing evidence has highlighted the involvement of the imbalance of long non-coding RNAs in the development of gastric cancer (GC), which is one of the most common malignancies in the world. This study aimed to determine the role of lncRNA WT1-AS in the progression of GC and explore its underlying mechanism.

Methods

The expression of lncRNA WT1-AS in gastric cancer tissues was detected using RT-qPCR. We knocked down the expression of WT1-AS in GC cells or treated them with rapamycin or both. Then, transwell assay and scratch assay were carried out to determine the migration of GC cells, and flow cytometry was carried out to determine the cell cycle. The immunofluorescence technique was used to determine the autophagy, and a tumor formation experiment was carried out to determine tumor growth . The expression of factors related to the PI3K/Akt/mTOR pathway was also measured by Western Blotting.

Results

In GC tissues and cells, lncRNA WT1-AS was underexpressed. Moreover, overexpression of lncRNA WT1-AS blocked the PI3K/Akt/mTOR pathway. Upregulation of lncRNA WT1-AS or inhibition of the PI3K/Akt/mTOR pathway suppressed cancer cell migration , leading to cell cycle arrest, and promoted autophagy while inhibiting tumor growth . It also reduced the expression levels of Ki-67, MMP2, MMP9, and VEGF. The WT1-AS+rapamycin group was the most prominent in all experiments.

Conclusion

The upregulation of lncRNA WT1-AS could suppress the PI3K/Akt/mTOR pathway, which inhibits cell migration and cell cycle arrest while promoting autophagy in gastric cancer cells.

This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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2024-11-08
2025-05-02
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References

  1. SongW. A novel prognostic model based on epithelial-mesenchymal transition-related genes predicts patient survival in gastric cancer.World J Surg Oncol.202119121610.1186/s12957‑021‑02329‑9
    [Google Scholar]
  2. NiuP.H. ZhaoL.L. WuH.L. ZhaoD.B. ChenY.T. Artificial intelligence in gastric cancer: Application and future perspectives.World J. Gastroenterol.202026365408541910.3748/wjg.v26.i36.540833024393
    [Google Scholar]
  3. Martínez-BarriocanalÁ. ArangoD. DopesoH. PVT1 Long Non-coding RNA in Gastrointestinal Cancer.Front. Oncol.2020103810.3389/fonc.2020.0003832083000
    [Google Scholar]
  4. TassinariM. RichterS.N. GandelliniP. Biological relevance and therapeutic potential of G-quadruplex structures in the human noncoding transcriptome.Nucleic Acids Res.20214973617363310.1093/nar/gkab12733721024
    [Google Scholar]
  5. XuT. LiuX. XiaR. YinL. KongR. ChenW. HuangM. ShuY. SP1-induced upregulation of the long noncoding RNA TINCR regulates cell proliferation and apoptosis by affecting KLF2 mRNA stability in gastric cancer.Oncogene201534455648566110.1038/onc.2015.1825728677
    [Google Scholar]
  6. SunM. XiaR. JinF. XuT. LiuZ. DeW. LiuX. Downregulated long noncoding RNA MEG3 is associated with poor prognosis and promotes cell proliferation in gastric cancer.Tumour Biol.20143521065107310.1007/s13277‑013‑1142‑z24006224
    [Google Scholar]
  7. XuT. HuangM. XiaR. LiuX. SunM. YinL. ChenW. HanL. ZhangE. KongR. DeW. ShuY. Decreased expression of the long non-coding RNA FENDRR is associated with poor prognosis in gastric cancer and FENDRR regulates gastric cancer cell metastasis by affecting fibronectin1 expression.J. Hematol. Oncol.2014716310.1186/s13045‑014‑0063‑725167886
    [Google Scholar]
  8. WangL.L. ZhangL. CuiX.F. RETRACTED: Downregulation of long noncoding RNA LINC01419 inhibits cell migration, invasion, and tumor growth and promotes autophagy via inactivation of the PI3K/Akt1/mTOR pathway in gastric cancer.Ther. Adv. Med. Oncol.201911175883591987465110.1177/175883591987465131579114
    [Google Scholar]
  9. ChenJ.F. STAT3-induced lncRNA HAGLROS overexpression contributes to the malignant progression of gastric cancer cells via mTOR signal-mediated inhibition of autophagy.Mol Cancer.201817116
    [Google Scholar]
  10. MayerI.A. ArteagaC.L. The PI3K/AKT Pathway as a Target for Cancer Treatment.Annu. Rev. Med.2016671112810.1146/annurev‑med‑062913‑05134326473415
    [Google Scholar]
  11. XuZ. HanX. OuD. LiuT. LiZ. JiangG. LiuJ. ZhangJ. Targeting PI3K/AKT/mTOR-mediated autophagy for tumor therapy.Appl. Microbiol. Biotechnol.2020104257558710.1007/s00253‑019‑10257‑831832711
    [Google Scholar]
  12. TanX. ZhangZ. YaoH. ShenL. RETRACTED: Tim-4 promotes the growth of colorectal cancer by activating angiogenesis and recruiting tumor-associated macrophages via the PI3K/AKT/mTOR signaling pathway.Cancer Lett.201843611912810.1016/j.canlet.2018.08.01230118845
    [Google Scholar]
  13. NepstadI. HatfieldK.J. GrønningsæterI.S. ReikvamH. The PI3K-Akt-mTOR Signaling Pathway in Human Acute Myeloid Leukemia (AML) Cells.Int. J. Mol. Sci.2020218290710.3390/ijms2108290732326335
    [Google Scholar]
  14. MiricescuD. TotanA. PI3K/AKT/mTOR signaling pathway in breast cancer: From molecular landscape to clinical aspects.Int J Mol Sci.2020221173
    [Google Scholar]
  15. TanA.C. Targeting the PI3K/Akt/mTOR pathway in non-small cell lung cancer (NSCLC).Thorac. Cancer202011351151810.1111/1759‑7714.1332831989769
    [Google Scholar]
  16. JiangC. MaZ. ZhangG. YangX. DuQ. WangW. CSNK2A1 Promotes Gastric Cancer Invasion Through the PI3K-Akt-mTOR Signaling Pathway.Cancer Manag. Res.201911101351014310.2147/CMAR.S22262031819646
    [Google Scholar]
  17. ZengL. LiaoQ. ZouZ. WenY. WangJ. LiuC. HeQ. WengN. ZengJ. TangH. FangR. LeiZ. TangZ. YangX. CuiS. Long non-coding RNA XLOC_006753 promotes the development of multidrug resistance in gastric cancer cells through the PI3K/AKT/mTOR signaling pathway.Cell. Physiol. Biochem.20185131221123610.1159/00049549930481766
    [Google Scholar]
  18. LeeH.J. Venkatarame Gowda SaralammaV. KimS.M. Pectolinarigenin induced cell cycle arrest, autophagy, and apoptosis in gastric cancer cell via PI3K/AKT/mTOR signaling pathway.Nutrients20181081043
    [Google Scholar]
  19. DuT. ZhangB. ZhangS. JiangX. ZhengP. LiJ. YanM. ZhuZ. LiuB. Decreased expression of long non-coding RNA WT1-AS promotes cell proliferation and invasion in gastric cancer.Biochim. Biophys. Acta Mol. Basis Dis.201618621121910.1016/j.bbadis.2015.10.00126449525
    [Google Scholar]
  20. PintoM.P. OwenG.I. RetamalI. GarridoM. Angiogenesis inhibitors in early development for gastric cancer.Expert Opin. Investig. Drugs20172691007101710.1080/13543784.2017.136192628770623
    [Google Scholar]
  21. KimK.Y. ParkK.I. KimS.H. YuS.N. ParkS.G. KimY. SeoY.K. MaJ.Y. AhnS.C. Inhibition of autophagy promotes salinomycin-induced apoptosis via reactive oxygen species-mediated PI3K/AKT/mTOR and ERK/p38 MAPK-dependent signaling in human prostate cancer cells.Int. J. Mol. Sci.2017185108810.3390/ijms1805108828524116
    [Google Scholar]
  22. ShengX. ZhuP. ZhaoY. ZhangJ. LiH. ZhaoH. QinJ. Effect of PI3K/AKT/mTOR signaling pathway on regulating and controlling the anti-invasion and metastasis of hepatoma cells by bufalin.Recent Patents Anticancer Drug Discov.2021161546510.2174/22123970MTEzaODMD433530915
    [Google Scholar]
  23. SunS. GDP induces PANC-1 human pancreatic cancer cell death preferentially under nutrient starvation by inhibiting PI3K/Akt/mTOR/ Autophagy signaling pathway.Chem Biodivers.2021189e2100389
    [Google Scholar]
  24. FattahiS. Amjadi-MohebF. TabaripourR. AshrafiG.H. Akhavan-NiakiH. PI3K/AKT/mTOR signaling in gastric cancer: Epigenetics and beyond.Life Sci.202026211851310.1016/j.lfs.2020.11851333011222
    [Google Scholar]
  25. RongL. LiZ. LengX. LiH. MaY. ChenY. SongF. Salidroside induces apoptosis and protective autophagy in human gastric cancer AGS cells through the PI3K/Akt/mTOR pathway.Biomed. Pharmacother.202012210972610.1016/j.biopha.2019.10972631918283
    [Google Scholar]
  26. PengY. QiuL. XuD. ZhangL. YuH. DingY. DengL. LinJ. M 4 IDP, a zoledronic acid derivative, induces G1 arrest, apoptosis and autophagy in HCT116 colon carcinoma cells via blocking PI3K/Akt/mTOR pathway.Life Sci.2017185637210.1016/j.lfs.2017.07.02428751160
    [Google Scholar]
  27. IppenF.M. GroschJ.K. SubramanianM. KuterB.M. LiedererB.M. PliseE.G. MoraJ.L. NayyarN. SchmidtS.P. Giobbie-HurderA. Martinez-LageM. CarterS.L. CahillD.P. WakimotoH. BrastianosP.K. Targeting the PI3K/Akt/mTOR pathway with the pan-Akt inhibitor GDC-0068 in PIK3CA-mutant breast cancer brain metastases.Neuro-oncol.201921111401141110.1093/neuonc/noz10531173106
    [Google Scholar]
  28. DuanS. HuangW. LiuX. LiuX. ChenN. XuQ. HuY. SongW. ZhouJ. IMPDH2 promotes colorectal cancer progression through activation of the PI3K/AKT/mTOR and PI3K/AKT/FOXO1 signaling pathways.J. Exp. Clin. Cancer Res.201837130410.1186/s13046‑018‑0980‑330518405
    [Google Scholar]
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  • Article Type:
    Research Article
Keyword(s): Autophagy; Gastric cancer; LncRNA WT1-AS; Migration; Overexpression; PI3K/Akt1/mTOR pathway
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