|Table of Contents|

Influences of isovitexin on the proliferation,apoptosis,migration and invasion of pancreatic cancer cells by regulating the miR-107/CCND1 axis

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 15
Page:
2756-2764
Research Field:
Publishing date:

Info

Title:
Influences of isovitexin on the proliferation,apoptosis,migration and invasion of pancreatic cancer cells by regulating the miR-107/CCND1 axis
Author(s):
XUAN Hongyan; KAN Xuan; ZHU Zhensheng
Department of Oncology,Jinan Hospital of Integrated Chinese and Western Medicine,Shandong Jinan 271100,China.
Keywords:
pancreatic cancer; isovitexin; microRNA-107; cyclin D1; proliferation; apoptosis; migration; invasion
PACS:
R735.9
DOI:
10.3969/j.issn.1672-4992.2023.15.002
Abstract:
Objective:To investigate the influences and molecular mechanism of isovitexin(IVX) on the proliferation,apoptosis,migration and invasion of pancreatic cancer(PCa) cells.Methods:Human PCa cell lines(PANC-1,AsPC-1,BxPC-3,Capan-1 and SW 1990) and human normal pancreatic ductal epithelial cells(HPDE) were cultured in vitro,the expression of microRNA-107(miR-107) and cyclin D1(CCND1) in cells was detected by quantitative real-time PCR(qRT-PCR) and Western blot.MTT assay was used to detect the toxicity of IVX on PANC-1 cells.PANC-1 cells were separated into normal control(NC) group,5 μmol/L IVX group,10 μmol/L IVX group,20 μmol/L IVX group,20 μmol/L IVX+anti-NC group and 20 μmol/L IVX+anti-miR-107 group.Cell clone formation assay was performed to detect cell proliferation activity.Flow cytometry was performed to detect apoptosis and cell cycle.Scratch healing assay and Transwell chamber assay were performed to detect cell migration and invasion.The targeting relationship between miR-107 and CCND1 in PANC-1 cells was verified by dual-luciferase reporter gene detection and RNA-binding protein immunoprecipitation(RIP) experiments.Nude mouse tumorigenesis experiments,immunohistochemistry(IHC) staining and qRT-PCR were performed to explore the influences of IVX on tumor growth and expression of Ki-67,CCND1 and miR-107 in PCa cells in vivo.Results:The expression of miR-107 was low and the expression of CCND1 was high in PCa cell line.IVX inhibited the proliferation of PANC-1 cells in a concentration-dependent manner.5,10 and 20 μmol/L IVX inhibited cell proliferation,migration and invasion in a concentration-dependent manner,induced cell cycle arrest and apoptosis,up-regulated miR-107 expression,and decreased CCND1 mRNA and protein levels(all P＜0.05).Down-regulating the expression of miR-107 could obviously reduce the inhibitory effect of IVX on the malignant biological behaviors of PCa cells.Dual-luciferase reporter assays and RIP experiments confirmed that CCND1 was a target of miR-107.The results of nude mice xenograft experiments showed that IVX could obviously inhibit the growth of xenografted tumors and the expression of Ki-67 and CCND1 in vivo,and up-regulated the expression of miR-107(all P＜0.05).Conclusion:IVX may inhibit the expression of CCND1 by up-regulating miR-107,thereby inhibiting the proliferation,migration and invasion of PCa cells and inducing apoptosis.

References:

[1] WOLRAB D,JIRASKO R,CIFKOVA E,et al.Lipidomic profiling of human serum enables detection of pancreatic cancer［J］.Nat Commun,2022,13(1):124-139.
[2] ZHOU C,LIANG Y,ZHOU L,et al.TSPAN1 promotes autophagy flux and mediates cooperation between WNT-CTNNB1 signaling and autophagy via the MIR454-FAM83A-TSPAN1 axis in pancreatic cancer［J］.Autophagy,2021,17(10):3175-3195.
[3] ZHOU JY,CHE JH,LU X,et al.MiR-320b inhibits pancreatic cancer cell proliferation by targeting FOXM1［J］.Curr Pharm Biotechnol,2021,22(8):1106-1113.
[4] IMAMURA T,KOMATSU S,ICHIKAWA D,et al.Depleted tumor suppressor miR-107 in plasma relates to tumor progression and is a novel therapeutic target in pancreatic cancer［J］.Sci Rep,2017,7(1):5708-5721.
[5] GONG J,LU X,XU J,et al.Coexpression of UCA1 and ITGA2 in pancreatic cancer cells target the expression of miR-107 through focal adhesion pathway［J］.J Cell Physiol,2019,234(8):12884-12896.
[6] VALLA M,KLAESTAD E,YTTERHUS B,et al.CCND1 amplification in breast cancer -associations with proliferation,histopathological grade,molecular subtype and prognosis［J］.J Mammary Gland Biol Neoplasia,2022,27(1):67-77.
[7] TAKAO K,KONISHI H,MATSUBARA D,et al.MiR-3663-3p inhibits the progression of gastric cancer through the CCND1 pathway［J］.Anticancer Res,2021,41(5):2441-2449.
[8] ZHANG H,HE C,GUO X,et al.DDX39B contributes to the proliferation of colorectal cancer through direct binding to CDK6/CCND1［J］.Cell Death Discov,2022,8(1):30-38.
[9] CHEN ZM,YU Q,CHEN G,et al.MiR-193a-3p inhibits pancreatic ductal adenocarcinoma cell proliferation by targeting CCND1［J］.Cancer Manag Res,2019,11:4825-4837.
[10] ZHU H,ZHAO N,JIANG M.Isovitexin attenuates tumor growth in human colon cancer cells through the modulation of apoptosis and epithelial-mesenchymal transition via PI3K/Akt/mTOR signaling pathway［J］.Biochem Cell Biol,2021,99(6):741-749.
[11] XU C,CAO X,CAO X,et al.Isovitexin inhibits stemness and induces apoptosis in hepatocellular carcinoma SK-Hep-1 spheroids by upregulating miR-34a expression［J］.Anticancer Agents Med Chem,2020,20(14):1654-1663.
[12] CHENG J,WANG G,ZHANG N,et al.Isovitexin modulates autophagy in Alzheimer's disease via miR-107 signalling［J］.Transl Neurosci,2020,11(1):391-401.
[13] 赵富周,丁成智,李晓明.异牡荆素对非小细胞性肺癌细胞自我更新和凋亡的影响［J］.中国临床药理学杂志,2022,38(3):219-223. ZHAO FZ,DING CZ,LI XM.Effect of isovitexin on self-renewal and apoptosis of non-small cell lung cancer cells［J］.Chinese Journal of Clinical Pharmacology,2022,38(3):219-223.
[14] QIE S,DIEHL JA.Cyclin D1,cancer progression,and opportunities in cancer treatment［J］.J Mol Med(Berl),2016,94(12):1313-1326.
[15] JEFFREYS SA,BECKER TM,KHAN S,et al.Prognostic and predictive value of CCND1/Cyclin D1 amplification in breast cancer with a focus on postmenopausal patients:a systematic review and meta-analysis［J］.Front Endocrinol(Lausanne),2022,13:895729.
[16] LIU B,YAN L,CHI Y,et al.Long non-coding RNA AFAP1-AS1 facilitates ovarian cancer progression by regulating the miR-107/PDK4 axis［J］.J Ovarian Res,2021,14(1):60-70.
[17] ZHOU J,SUN X,ZHANG X,et al.miR-107 is involved in the regulation of NEDD9-mediated invasion and metastasis in breast cancer［J］.BMC Cancer,2022,22(1):533-545.
[18] ZHAO M,WANG Y,JIANG C,et al.miR-107 regulates the effect of MCM7 on the proliferation and apoptosis of colorectal cancer via the PAK2 pathway［J］.Biochem Pharmacol,2021,190:114610.

Memo

Memo:
山东省中医药科技项目（编号：Z-2022003）
Last Update: 2023-06-30