Basic research

Effects of knockdown of immunoregulatory protein B7-H3 gene on malignant proliferation, invasion and stem cell-like characteristics of bladder cancer cells

  • Xiao-han WANG ,
  • Yun-lin YE ,
  • Kang-hua XIAO ,
  • Zhi-xin ZHAO ,
  • Jing-ya WU
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  • 1.Department of surgery, Henan Vocational College of nursing, Anyang 455000, China
    2.Department of Urology and oncology, Cancer Hospital Affiliated to Zhongshan University, Guangzhou 510030, China
    3.Pharmacy teaching and Research Office, Henan Vocational College of nursing, Anyang 455000, China
    4.Department of traditional Chinese medicine, Henan Province Anyang District Hospital, Anyang 455000, China
WANG Xiao-han, E-mail: wang136473@163.com.

Online published: 2021-12-03

Supported by

2018 Henan Province Medical Science and Technology Tackling Project(2018020950)

Abstract

Objective

·To investigate the effect of gene interfering with immune regulatory protein B7-H3 on malignant proliferation and stemness characteristics of bladder cancer J82 cells.

Methods

·Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect shRNA interference efficiency. The proliferation of J82 cells was detected by clone formation assay. Cell apoptosis was detected by flow cytometry. Cell invasion was detected using Transwell asssay. The tumor-cloning ability was observed using tumor sphere formation experiment. Apoptosis, invasion, and expression and stemness-related proteins were detected by Western blotting.

Results

·B7-H3 is highly expressed in bladder cancer tissues and bladder cancer cell lines (P=0.000). shRNA2 was identified as the most efficient interference with B7-H3 gene in three shRNAs (P=0.000). The interference of B7-H3 inhibited the proliferation, invasion, tumor cloning ability and stem cell-like characteristics of J82 cells (P=0.000). Furthermore, B7-H3 interference promoted the apoptosis of J82 cells (P=0.000).

Conclusion

·The gene interference of immunoregulatory protein B7-H3 can inhibit the malignant proliferation, invasion and stemness characteristics of bladder cancer J82 cells, providing a new possibility and effective evidence for the treatment of bladder cancer.

Cite this article

Xiao-han WANG , Yun-lin YE , Kang-hua XIAO , Zhi-xin ZHAO , Jing-ya WU . Effects of knockdown of immunoregulatory protein B7-H3 gene on malignant proliferation, invasion and stem cell-like characteristics of bladder cancer cells[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2021 , 41(11) : 1454 -1460 . DOI: 10.3969/j.issn.1674-8115.2021.11.008

References

1 Sanli O, Dobruch J, Knowles MA, et al. Bladder cancer[J]. Nat Rev Dis Primers, 2017, 3: 17022.
2 白志鹏, 唐以众. TURBT联合表柔比星与羟喜树碱膀胱灌注对浅表性膀胱癌患者术后复发率及生活质量的影响[J]. 解放军医药杂志, 2019, 31(4): 40-43.
3 DeGeorge KC, Holt HR, Hodges SC. Bladder cancer: diagnosis and treatment[J]. Am Fam Physician, 2017, 96(8): 507-514.
4 Burger M, Catto JW, Dalbagni G, et al. Epidemiology and risk factors of urothelial bladder cancer[J]. Eur Urol, 2013, 63(2): 234-241.
5 Godfrey DI, Le Nours J, Andrews DM, et al. Unconventional T cell targets for cancer immunotherapy[J]. Immunity, 2018, 48(3): 453-473.
6 Ward-Kavanagh LK, Lin WW, ?edy JR, et al. The TNF receptor superfamily in Co-stimulating and Co-inhibitory responses[J]. Immunity, 2016, 44(5): 1005-1019.
7 Janakiram M, Shah UA, Liu W, et al. The third group of the B7-CD28 immune checkpoint family: HHLA2, TMIGD2, B7x, and B7-H3[J]. Immunol Rev, 2017, 276(1): 26-39.
8 Wang Z, Wang Z, Zhang C, et al. Genetic and clinical characterization of B7-H3 (CD276) expression and epigenetic regulation in diffuse brain glioma[J]. Cancer Sci, 2018, 109(9): 2697-2705.
9 Kang FB, Wang L, Jia HC, et al. B7-H3 promotes aggression and invasion of hepatocellular carcinoma by targeting epithelial-to-mesenchymal transition via JAK2/STAT3/Slug signaling pathway[J]. Cancer Cell Int, 2015, 15:45.
10 刘新波, 康富标, 曹娜娜, 等. B7-H3分子表达与食管癌复发转移的相关性研究[J]. 解放军医药杂志, 2019, 31(10): 23-26, 35.
11 Inamura K, Takazawa Y, Inoue Y, et al. Tumor B7-H3 (CD276) expression and survival in pancreatic cancer[J]. J Clin Med, 2018, 7(7):172.
12 Li YC, Guo GN, Song J, et al. B7-H3 promotes the migration and invasion of human bladder cancer cells via the PI3K/Akt/STAT3 signaling pathway[J]. J Cancer, 2017, 8(5): 816-824.
13 Xu ZL, Zhang Y, Wang L, et al. B7?H3 promotes malignant progression of muscle?invasive bladder cancer[J]. Oncol Rep, 2018, 40(5): 2722-2733.
14 Flem-Karlsen K, Fodstad ?, Tan M, et al. B7-H3 in cancer-beyond immune regulation[J]. Trends Cancer, 2018, 4(6): 401-404.
15 Zhong C, Tao B, Chen Y, et al. B7-H3 regulates glioma growth and cell invasion through a JAK2/STAT3/Slug-dependent signaling pathway[J]. Onco Targets Ther, 2020, 13:2215-2224.
16 Wang L, Zhang Q, Chen W, et al. B7-H3 is overexpressed in patients suffering osteosarcoma and associated with tumor aggressiveness and metastasis[J]. PloS one, 2013, 8(8):e70689.
17 Li DB, Wang J, Zhou J, et al. B7-H3 combats apoptosis induced by chemotherapy by delivering signals to pancreatic cancer cells[J]. Oncotarget, 2017, 8(43): 74856-74868.
18 Dawood S, Austin L, Cristofanilli M. Cancer stem cells: implications for cancer therapy[J]. Oncology (Williston Park), 2014, 28(12): 1101-1107, 1110.
19 Nassar D, Blanpain C. Cancer stem cells: basic concepts and therapeutic implications[J]. Annu Rev Pathol, 2016, 11: 47-76.
20 Vlashi E, Pajonk F. Cancer stem cells, cancer cell plasticity and radiation therapy[J]. Semin Cancer Biol, 2015, 31: 28-35.
21 Liu ZX, Zhang WL, Phillips JB, et al. Immunoregulatory protein B7-H3 regulates cancer stem cell enrichment and drug resistance through MVP-mediated MEK activation[J]. Oncogene, 2019, 38(1): 88-102.
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