Curcumin Inhibits the Proliferation, Migration, Invasion, and Apoptosis of Diffuse Large B-Cell Lymphoma Cell Line by Regulating MiR-21/VHL Axis
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Purpose: Curcumin exerts its anti-cancer effects, partly by targeting special microRNAs, in human cancers. MiR-21 is a key oncomirin carcinogenesis of multiple human cancers. Here, we aimed to further explore the mechanistic insight into the link betweencurcumin and miR-21 on diffuse large B-cell lymphoma (DLBCL). Materials and Methods: Quantitative real-time PCR assays were performed to assess the levels of miR-21 and Von Hippel-Lindau(VHL) mRNA. In situ hybridization assay was used for miR-21 expression visualization in lymphoma tissues. Western blot was usedfor determination of VHL protein, Ki-67, caspase-3, and cleaved caspase-3 levels. Dual-luciferase reporter assay and RNA immunoprecipitationassay were employed to confirm the direct target of miR-21. MTT assay, flow cytometric analysis, and transwell assaywere used to evaluate cell proliferation, apoptosis, and migration and invasion capacities, respectively. Results: Curcumin repressed the proliferation, migration, and invasion abilities and promoted apoptosis in SU-DHL-8 cells. Curcumininhibited miR-21 expression and curcumin exerted its anti-proliferation, anti-migration, anti-invasion, and pro-apoptosiseffects by miR-21 in SU-DHL-8 cells. VHL was a direct target of miR-21. Moreover, curcumin exerted its regulatory effects on SUDHL-8 cells by VHL. Conclusion: Curcumin exerted its anti-proliferation, anti-migration, anti-invasion, and pro-apoptosis functions, at least partly, byrepressing miR-21 and regulating VHL expression in DLBCL cell line. Our findings provided a possible molecular mechanism ofcurcumin-mediated anti-cancer effect.
Abstract
Purpose: Curcumin exerts its anti-cancer effects, partly by targeting special microRNAs, in human cancers. MiR-21 is a key oncomirin carcinogenesis of multiple human cancers. Here, we aimed to further explore the mechanistic insight into the link betweencurcumin and miR-21 on diffuse large B-cell lymphoma (DLBCL). Materials and Methods: Quantitative real-time PCR assays were performed to assess the levels of miR-21 and Von Hippel-Lindau(VHL) mRNA. In situ hybridization assay was used for miR-21 expression visualization in lymphoma tissues. Western blot was usedfor determination of VHL protein, Ki-67, caspase-3, and cleaved caspase-3 levels. Dual-luciferase reporter assay and RNA immunoprecipitationassay were employed to confirm the direct target of miR-21. MTT assay, flow cytometric analysis, and transwell assaywere used to evaluate cell proliferation, apoptosis, and migration and invasion capacities, respectively. Results: Curcumin repressed the proliferation, migration, and invasion abilities and promoted apoptosis in SU-DHL-8 cells. Curcumininhibited miR-21 expression and curcumin exerted its anti-proliferation, anti-migration, anti-invasion, and pro-apoptosiseffects by miR-21 in SU-DHL-8 cells. VHL was a direct target of miR-21. Moreover, curcumin exerted its regulatory effects on SUDHL-8 cells by VHL. Conclusion: Curcumin exerted its anti-proliferation, anti-migration, anti-invasion, and pro-apoptosis functions, at least partly, byrepressing miR-21 and regulating VHL expression in DLBCL cell line. Our findings provided a possible molecular mechanism ofcurcumin-mediated anti-cancer effect.
참고문헌 (40)
- Martelli M, "Diffuse large B-cell lymphoma", Crit Rev Oncol Hematol, 87, pp.146~171 (2013)
- Shaffer AL 3rd, "Pathogenesis of human B cell lymphomas", Annu Rev Immunol, 30, pp.565~610 (2012)
- Tilly H, "Diffuse large B-cell lymphoma (DLBCL): ESMO Clinical Practice Guidelines for diagnosis, treatment and followup", Ann Oncol, 26(Suppl 5), pp.v116~v125 (2015)
- Nabavi SF, "Curcumin : a natural product for diabetes and its complications", Curr Top Med Chem, 15, pp.2445~2455 (2015)
- Liu CH, "Antimicrobial activity of curcumin-loaded myristic acid microemulsions against Staphylococcus epidermidis", Chem Pharm Bull(Tokyo), 60, pp.1118~1124 (2012)
- Meng B, "Antioxidant and antiinflammatory activities of curcumin on diabetes mellitus and its complications", Curr Pharm Des, 19, pp.2101~2113 (2013)
- Lüer S, "Antibacterial and antiinflammatory kinetics of curcumin as a potential antimucositis agent in cancer patients", Nutr Cancer, 64, pp.975~981 (2012)
- Hashish EA, "Hepatoprotective and nephroprotective effect of curcumin against copper toxicity in rats", Indian J Clin Biochem, 31, pp.270~277 (2016)
- Lin J, "Curcumin diminishes the impacts of hyperglycemia on the activation of hepatic stellate cells by suppressing membrane translocation and gene expression of glucose transporter-2", Mol Cell Endocrinol, 333, pp.160~171 (2011)
- Mudduluru G, "Curcumin regulates miR-21 expression and inhibits invasion and metastasis in colorectal cancer", Biosci Rep, 31, pp.185~197 (2011)
- Toden S, "Curcumin mediates chemosensitization to 5-fluorouracil through miRNA-induced suppression of epithelial-to-mesenchymal transition in chemoresistant colorectal cancer", Carcinogenesis, 36, pp.355~367 (2015)
- Pandey A, "Berberine and curcumin target survivin and STAT3 in gastric cancer cells and synergize actions of standard chemotherapeutic 5-fluorouracil", Nutr Cancer, 67, pp.1293~1304 (2015)
- Hammond SM, "An overview of microRNAs", Adv Drug Deliv Rev, 87, pp.3~14 (2015)
- Reddy KB, "MicroRNA(miRNA)in cancer", Cancer Cell Int, 15, pp.38~ (2015)
- Hayes J, "MicroRNAs in cancer : biomarkers, functions and therapy", Trends Mol Med, 20, pp.460~469 (2014)
- Simonian M, "Circulating miR-21 as novel biomarker in gastric cancer : diagnostic and prognostic biomarker", J Cancer Res Ther, 14, pp.475~ (2018)
- Frankel LB, "Programmed cell death 4(PDCD4)is an important functional target of the microRNA miR-21 in breast cancer cells", J Biol Chem, 283, pp.1026~1033 (2008)
- Chan JK, "The inhibition of miR-21 promotes apoptosis and chemosensitivity in ovarian cancer", Gynecol Oncol, 132, pp.739~744 (2014)
- Cui Q, "Circulating cell-free miR-494 and miR-21 are disease response biomarkers associated with interim-positron emission tomography response in patients with diffuse large B-cell lymphoma", Oncotarget, 9, pp.34644~34657 (2018)
- Li J, "miR-21 expression predicts prognosis in diffuse large B-cell lymphoma", Int J Clin Exp Pathol, 8, pp.15019~15024 (2015)
- Go H, "MicroRNA-21 plays an oncogenic role by targeting FOXO1 and activating the PI3K", AKT pathway in diffuse large B-cell lymphoma, 2015, pp.6, 15035~15049
- Fu R, "Aberrant overexpression and regulatory mechanism of mir-21 in diffuse large B cell lymphoma", Am Soc Hematology, 124, pp.5171~ (2014)
- Ali S, "Gemcitabine sensitivity can be induced in pancreatic cancer cells through modulation of miR-200 and miR-21 expression by curcumin or its analogue CDF", Cancer Res, 70, pp.3606~3617 (2010)
- Wilken R, "Curcumin : a review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma", Mol Cancer, 10, pp.12~ (2011)
- Ye M, "Curcumin promotes apoptosis by activating the p53-miR-192-5p", 215-XIAP pathway in non-small cell lung cancer, 2015, pp.357, 196~205
- Epelbaum R, "Curcumin and gemcitabine in patients with advanced pancreatic cancer", Nutr Cancer, 62, pp.1137~1141 (2010)
- Bansal SS, "Advanced drug delivery systems of curcumin for cancer chemoprevention", Cancer Prev Res(Phila), 4, pp.1158~1171 (2011)
- Li Y, "Targeting cancer stem cells by curcumin and clinical applications", Cancer Lett, 346, pp.197~205 (2014)
- Bassiouny AR, "Curcumin and EGCG suppress apurinic", apyrimidinic endonuclease 1 and induce complete remission in B-cell non-Hodgkin’s lymphoma patients, 2011, pp.1, 525~544
- Pancione M, "Immune escape mechanisms in colorectal cancer pathogenesis and liver metastasis", J Immunol Res, 2014, pp.686879~ (2014)
- Saini S, "Curcumin modulates microRNA-203-mediated regulation of the Src-Akt axis in bladder cancer", Cancer Prev Res(Phila), 4, pp.1698~1709 (2011)
- Taverna S, "Curcumin inhibits in vitro and in vivo chronic myelogenous leukemia cells growth : a possible role for exosomal disposal of miR-21", Oncotarget, 6, pp.21918~21933 (2015)
- Chen W, "Clinical significance and detection of microRNA-21 in serum of patients with diffuse large B-cell lymphoma in Chinese population", Eur J Haematol, 92, pp.407~412 (2014)
- Liu K, "MicroRNA-21 regulates the viability and apoptosis of diffuse large B-cell lymphoma cells by upregulating B cell lymphoma-2", Exp Ther Med, 14, pp.4489~4496 (2017)
- Moore LE, "Von Hippel-Lindau(VHL)inactivation in sporadic clear cell renal cancer : associations with germline VHL polymorphisms and etiologic risk factors", PLoS Genet, 7, pp.e1002312~ (2011)
- Kong W, "Upregulation of miRNA-155 promotes tumour angiogenesis by targeting VHL and is associated with poor prognosis and triple-negative breast cancer", Oncogene, 33, pp.679~689 (2014)
- Amara K, "Prognostic significance of aberrant promoter hypermethylation of CpG islands in patients with diffuse large B-cell lymphomas", Ann Oncol, 19, pp.1774~1786 (2008)
- Zhang KL, "Blockage of a miR-21", EGFR regulatory feedback loop augments anti-EGFR therapy in glioblastomas, 2014, pp.342, 139~149
- Wang Y, "Suppression of the growth and invasion of human head and neck squamous cell carcinomas via regulating STAT3 signaling and the miR-21", β-catenin axis with HJC0152, 2017, pp.16, 578~590
- Sikora E, "Inhibition of proliferation and apoptosis of human and rat T lymphocytes by curcumin, a curry pigment", Biochem Pharmacol, 54, pp.899~907 (1997)