Knockdown of lncRNA MEG 8 inhibits cell proliferation and invasion , but promotes cell apoptosis in hemangioma , via miR ‐ 203 ‐ induced mediation of the Notch signaling pathway

as a member of the long non‐coding (lnc)rna family, lncrna maternally expressed 8, small nucleolar rna host gene (MEG8), has been reported to serve an oncogenic role in several types of malignancies, including hepatocel‐ lular carcinoma, non‐small cell lung cancer and pancreatic cancer. The current study aimed to investigate the effect of the knockdown of MEG8 on human hemangioma endothelial cell (Hemec) proliferation, apoptosis and invasion, in addi‐ tion to determining the underlying molecular mechanism. The knockdown of lncRNA MEG8 was achieved by transfecting lncRNA MEG8 small interfering (si)rna into Hemecs, while the combined knockdown of lncrna MeG8 knockdown and microrna (mir)‐203 was established by co‐transfecting lncRNA MEG8 sirna and a mir‐203 inhibitor into Hemecs. The cell proliferation, apoptosis and invasion and the expres‐ sion levels of mir‐34a, miR‐200b, miR‐200b and notch signaling pathway‐related factors were detected via ccK‐8 Kit, flow cytometry, Transwell, reverse transcription‐quantitative Pcr and western blot assay, respectively. The knockdown of lncRNA MEG8 significantly inhibited proliferation (P<0.05) and invasion (P<0.05), but promoted apoptosis (P<0.01) in Hemecs. Furthermore, lncRNA MEG8 knockdown upregu‐ lated miR‐203 (P<0.01) expression, but did not alter miR‐34a or miR‐200b expression (both P>0.05). Subsequent experi‐ ments revealed that miR‐203 silencing exerted no significant effect on the expression levels of lncRNA MEG8 (P>0.05) in Hemecs. in addition, miR‐203 silencing increased cell proliferation (P<0.05) and invasion (P<0.01), but suppressed apoptosis (P<0.05). miR‐203 silencing also reversed the effect of lncRNA MEG8 knockdown on the proliferation (P<0.05), apoptosis (P<0.001) and invasion (P<0.01) of HemECs. Moreover, lncRNA MEG8 knockdown downregulated jagged canonical notch ligand 1 (JAG1; P<0.05) and Notch1 (P<0.05) expression levels, while miR‐203 silencing upregulated JaG1 (P<0.01) and Notch1 (P<0.01) expression levels and reversed the effects of lncRNA MEG8 knockdown on JAG1 (P<0.01) and Notch1 (P<0.01) expression in HemECs. In conclusion, the findings of the present study suggested that lncRNA MEG8 knockdown may inhibit cell proliferation and invasion, but promote cell apoptosis in hemangioma via miR‐203‐induced mediation of the notch signaling pathway.

[1]  Wenjun Shao,et al.  LncRNA IGFL2-AS1 Promotes the Proliferation, Migration, and Invasion of Colon Cancer Cells and is Associated with Patient Prognosis , 2021, Cancer management and research.

[2]  Peng Wang,et al.  The LncRNA MIR503HG/miR-224-5p/TUSC3 Signaling Cascade Suppresses Gastric Cancer Development via Modulating ATF6 Branch of Unfolded Protein Response , 2021, Frontiers in Oncology.

[3]  Bo-yuan Huang,et al.  LncRNA MEG8 promotes NSCLC progression by modulating the miR-15a-5p-miR-15b-5p/PSAT1 axis , 2021, Cancer Cell International.

[4]  R. Dong,et al.  LncRNA MEG8 plays an oncogenic role in hepatocellular carcinoma progression through miR-367-3p/14-3-3ζ/TGFβR1 axis. , 2020, Neoplasma.

[5]  S. Varambally,et al.  EZH2-Targeted Therapies in Cancer: Hype or a Reality , 2020, Cancer Research.

[6]  G. Strub,et al.  NOTCH Pathway Activation in Infantile Hemangiomas. , 2020, Journal of vascular surgery. Venous and lymphatic disorders.

[7]  M. Valdebran,et al.  Hemangioma-related syndromes. , 2020, Current opinion in pediatrics.

[8]  G. Richter,et al.  Hemangioma: Recent Advances , 2019, F1000Research.

[9]  Ting Chen,et al.  LncRNA Meg8 suppresses activation of hepatic stellate cells and epithelial-mesenchymal transition of hepatocytes via the Notch pathway. , 2019, Biochemical and biophysical research communications.

[10]  Jichun Yang,et al.  Long Non-Coding RNA in the Pathogenesis of Cancers , 2019, Cells.

[11]  Zhuo Zhao,et al.  LncRNA MEG8 regulates vascular smooth muscle cell proliferation, migration and apoptosis by targeting PPARα. , 2019, Biochemical and biophysical research communications.

[12]  Weiliang Jiang,et al.  lncRNA CASC9 regulates cell migration and invasion in hemangioma endothelial cells by targeting miR-125a-3p/Nrg1 , 2019, OncoTargets and therapy.

[13]  Minoru Terashima,et al.  MEG8 long noncoding RNA contributes to epigenetic progression of the epithelial-mesenchymal transition of lung and pancreatic cancer cells , 2018, The Journal of Biological Chemistry.

[14]  Wei Li,et al.  miR-203 inhibits ovarian tumor metastasis by targeting BIRC5 and attenuating the TGFβ pathway , 2018, Journal of Experimental & Clinical Cancer Research.

[15]  Qing Sun,et al.  miR-203 facilitates tumor growth and metastasis by targeting fibroblast growth factor 2 in breast cancer , 2016, OncoTargets and therapy.

[16]  Qiang Wang,et al.  Long noncoding RNA expression profile of infantile hemangioma identified by microarray analysis , 2016, Tumor Biology.

[17]  Melissa J. Fullwood,et al.  Roles, Functions, and Mechanisms of Long Non-coding RNAs in Cancer , 2016, Genom. Proteom. Bioinform..

[18]  Yi Ji,et al.  Signaling pathways in the development of infantile hemangioma , 2014, Journal of Hematology & Oncology.

[19]  E. Boscolo,et al.  Endothelial progenitor cells from infantile hemangioma and umbilical cord blood display unique cellular responses to endostatin. , 2006, Blood.

[20]  Thomas D. Schmittgen,et al.  Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. , 2001, Methods.

[21]  Si-Ming Yuan,et al.  The adipogenesis in infantile hemangioma and the expression of adipogenic-related genes. , 2017, International journal of clinical and experimental pathology.