hsa‑miR‑429 targets CBX8 to promote cell apoptosis in diffuse large B‑cell lymphoma

Liang,Yan; Yu,Zhuo-Jun; Liu,Min; Liu,Hui-Min; Zhang,Jiang-Zhao; Xiong,Tao; Tang,Yuan-Yan; Huang,Zhi-Ping

doi:10.3892/mmr.2021.12497

hsa‑miR‑429 targets CBX8 to promote cell apoptosis in diffuse large B‑cell lymphoma

Authors:
- Yan Liang
- Zhuo-Jun Yu
- Min Liu
- Hui-Min Liu
- Jiang-Zhao Zhang
- Tao Xiong
- Yuan-Yan Tang
- Zhi-Ping Huang
View Affiliations

Affiliations: Department of Hematology, Jingzhou Central Hospital, Institute of Hematology, Yangtze University, Jingzhou, Hubei 434020, P.R. China
Published online on: October 14, 2021 https://doi.org/10.3892/mmr.2021.12497
Article Number: 857
Copyright: © Liang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Diffuse large B‑cell lymphoma (DLBCL) is the most common type of non‑Hodgkin lymphoma worldwide. Several studies have indicated that Homo sapiens (hsa)‑microRNA (miR)‑429 exerts a tumor‑suppressive effect on a variety of malignant tumors. To the best of our knowledge, the molecular function and mechanism of action of hsa‑miR‑429 in DLBCL have not been evaluated to date. The present study demonstrated that the expression of hsa‑miR‑429 in DLBCL cells was significantly reduced. hsa‑miR‑429 inhibited the proliferation of the DLBCL cell lines, SUDHL‑4 and DB, and promoted apoptosis. A dual luciferase reporter assay was used to demonstrate that chromobox 8 (CBX8) was the target gene of hsa‑miR‑429. Overexpression of CBX8 promoted the proliferation of SUDHL‑4 and DB cells and inhibited apoptosis, thereby playing a cancer‑promoting role. Transfection of hsa‑miR‑429 mimic into DB cells overexpressing CBX8 antagonized the effect of CBX8 on the proliferation of DB cells. Moreover, the apoptotic rate was increased in DB cells overexpressing CBX8 and transfected with hsa‑miR‑429 mimic, while the proportion of cells in the G₂/M phase was significantly reduced. These results demonstrated the antagonistic effect of hsa‑miR‑429 on the oncogenic function of CBX8. Therefore, in DLBCL, the tumor suppressor effect of hsa‑miR‑429 may be achieved by targeted downregulation of CBX8, suggesting that hsa‑miR‑429 may be used as a diagnostic marker and a potential nucleic acid drug for DLBCL. CBX8 may also represent an effective therapeutic target for DLBCL.

View Figures

View References

1	Sehn LH and Gascoyne RD: Diffuse large B-cell lymphoma: Optimizing outcome in the context of clinical and biologic heterogeneity. Blood. 125:22–32. 2015. View Article : Google Scholar : PubMed/NCBI
2	Sehn LH and Salles G: Diffuse large B-cell lymphoma. N Engl J Med. 384:842–858. 2021. View Article : Google Scholar : PubMed/NCBI
3	Maltby S, Plank M, Ptaschinski C, Mattes J and Foster PS: MicroRNA function in mast cell biology: Protocols to characterize and modulate microRNA expression. Methods Mol Biol. 1220:287–304. 2015. View Article : Google Scholar : PubMed/NCBI
4	Hata A and Lieberman J: Dysregulation of microRNA biogenesis and gene silencing in cancer. Sci Signal. 8:re32015. View Article : Google Scholar : PubMed/NCBI
5	Cheng CJ, Bahal R, Babar IA, Pincus Z, Barrera F, Liu C, Svoronos A, Braddock DT, Glazer PM, Engelman DM, et al: MicroRNA silencing for cancer therapy targeted to the tumour microenvironment. Nature. 518:107–110. 2015. View Article : Google Scholar : PubMed/NCBI
6	Xue H and Tian GY: miR-429 regulates the metastasis and EMT of HCC cells through targeting RAB23. Arch Biochem Biophys. 637:48–55. 2018. View Article : Google Scholar : PubMed/NCBI
7	Guo C, Zhao D, Zhang Q, Liu S and Sun MZ: miR-429 suppresses tumor migration and invasion by targeting CRKL in hepatocellular carcinoma via inhibiting Raf/MEK/ERK pathway and epithelial-mesenchymal transition. Sci Rep. 8:23752018. View Article : Google Scholar : PubMed/NCBI
8	Zhang C, Chang C, Gao H, Wang Q, Zhang F and Xu C: miR-429 regulates rat liver regeneration and hepatocyte proliferation by targeting JUN/MYC/BCL2/CCND1 signaling pathway. Cell Signal. 50:80–89. 2018. View Article : Google Scholar : PubMed/NCBI
9	Zhang M, Dong BB, Lu M, Zheng MJ, Chen H, Ding JZ, Xu AM and Xu YH: miR-429 functions as a tumor suppressor by targeting FSCN1 in gastric cancer cells. OncoTargets Ther. 9:1123–1133. 2016.PubMed/NCBI
10	Wu CL, Ho JY, Hung SH and Yu DS: miR-429 expression in bladder cancer and its correlation with tumor behavior and clinical outcome. Kaohsiung J Med Sci. 34:335–340. 2018. View Article : Google Scholar : PubMed/NCBI
11	Yang J, Liu Y, He A, Liu Y, Wu J, Liao X, Lv Z, Wang F and Mei H: hsa-miR-429 promotes bladder cancer cell proliferation via inhibiting CDKN2B. Oncotarget. 8:68721–68729. 2017. View Article : Google Scholar : PubMed/NCBI
12	Deng Y, Luan F, Zeng L, Zhang Y and Ma K: miR-429 suppresses the progression and metastasis of osteosarcoma by targeting ZEB1. EXCLI J. 16:618–627. 2017.PubMed/NCBI
13	Wang HF, Wang WH, Zhuang HW and Xu M: miR-429 regulates the proliferation and apoptosis of nephroblastoma cells through targeting c-myc. Eur Rev Med Pharmacol Sci. 22:5172–5179. 2018.PubMed/NCBI
14	Liu D, Song L, Dai Z, Guan H, Kang H, Zhang Y, Yan W, Zhao X and Zhang S: miR-429 suppresses neurotrophin-3 to alleviate perineural invasion of pancreatic cancer. Biochem Biophys Res Commun. 505:1077–1083. 2018. View Article : Google Scholar : PubMed/NCBI
15	Zong M, Liu Y, Zhang K, J Y and Chen L: The effects of miR-429 on cell migration and invasion by targeting Slug in esophageal squamous cell carcinoma. Pathol Res Pract. 215:1525262019. View Article : Google Scholar : PubMed/NCBI
16	Wang Y, Liu J, Yao Q, Wang Y, Liu Z and Zhang L: LncRNA SNHG6 promotes Wilms' tumor progression through regulating miR-429/FRS2 axis. Cancer Biother Radiopharm. Jan 22–2021.(Epub ahead of print). View Article : Google Scholar
17	Zhang L, Liu Q, Mu Q, Zhou D, Li H, Zhang B and Yin C: miR-429 suppresses proliferation and invasion of breast cancer via inhibiting the Wnt/β-catenin signaling pathway. Thorac Cancer. 11:3126–3138. 2020. View Article : Google Scholar : PubMed/NCBI
18	Cava C, Novello C, Martelli C, Lodico A, Ottobrini L, Piccotti F, Truffi M, Corsi F, Bertoli G and Castiglioni I: Theranostic application of miR-429 in HER²⁺ breast cancer. Theranostics. 10:50–61. 2020. View Article : Google Scholar : PubMed/NCBI
19	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
20	Zhang CZ, Chen SL, Wang CH, He YF, Yang X, Xie D and Yun JP: CBX8 exhibits oncogenic activity via AKT/β-catenin activation in hepatocellular carcinoma. Cancer Res. 78:51–63. 2018. View Article : Google Scholar : PubMed/NCBI
21	Tang B, Tian Y, Liao Y, Li Z, Yu S, Su H, Zhong F, Yuan G, Wang Y, Yu H, et al: CBX8 exhibits oncogenic properties and serves as a prognostic factor in hepatocellular carcinoma. Cell Death Dis. 10:522019. View Article : Google Scholar : PubMed/NCBI
22	Xiao L, Zhou Z, Li W, Peng J, Sun Q, Zhu H, Song Y, Hou JL, Sun J, Cao HC, et al: Chromobox homolog 8 (CBX8) Interacts with Y-Box binding protein 1 (YBX1) to promote cellular proliferation in hepatocellular carcinoma cells. Aging (Albany NY). 11:7123–7149. 2019. View Article : Google Scholar : PubMed/NCBI
23	Zhang Y, Chen H, Zhu H and Sun X: CBX8 promotes tumorigenesis and confers radioresistance in esophageal squamous cell carcinoma cells through targeting APAF1. Gene. 711:1439492019. View Article : Google Scholar : PubMed/NCBI
24	Xiao W, Ou C, Qin J, Xing F, Sun Y, Li Z and Qiu J: CBX8, a novel DNA repair protein, promotes tumorigenesis in human esophageal carcinoma. Int J Clin Exp Pathol. 7:4817–4826. 2014.PubMed/NCBI
25	Tang J, Wang G, Zhang M, Li FY, Sang Y, Wang B, Hu K, Wu Y, Luo R, Liao D, et al: Paradoxical role of CBX8 in proliferation and metastasis of colorectal cancer. Oncotarget. 5:10778–10790. 2014. View Article : Google Scholar : PubMed/NCBI
26	Lee SH, Um SJ and Kim EJ: CBX8 suppresses Sirtinol-induced premature senescence in human breast cancer cells via cooperation with SIRT1. Cancer Lett. 335:397–403. 2013. View Article : Google Scholar : PubMed/NCBI
27	Lee SH, Um SJ and Kim EJ: CBX8 antagonizes the effect of Sirtinol on premature senescence through the AKT-RB-E2F1 pathway in K562 leukemia cells. Biochem Biophys Res Commun. 469:884–890. 2016. View Article : Google Scholar : PubMed/NCBI
28	Zeng F, Luo L, Li D, Guo J and Guo M: KPNA2 interaction with CBX8 contributes to the development and progression of bladder cancer by mediating the PRDM1/c-FOS pathway. J Transl Med. 19:1122021. View Article : Google Scholar : PubMed/NCBI
29	Wang S, Tailor K and Kwabi-Addo B: Androgen-induced epigenetic profiles of polycomb and trithorax genes in prostate cancer cells. Anticancer Res. 40:2559–2565. 2020. View Article : Google Scholar : PubMed/NCBI