CD9 knockdown suppresses cell proliferation, adhesion, migration and invasion, while promoting apoptosis and the efficacy of chemotherapeutic drugs and imatinib in Ph+ ALL SUP‑B15 cells

Xing,Chongyun; Xu,Wanling; Shi,Yifen; Zhou,Bin; Wu,Dijiong; Liang,Bin; Zhou,Yuhong; Gao,Shenmeng; Feng,Jianhua

doi:10.3892/mmr.2020.11350

CD9 knockdown suppresses cell proliferation, adhesion, migration and invasion, while promoting apoptosis and the efficacy of chemotherapeutic drugs and imatinib in Ph+ ALL SUP‑B15 cells

Authors:
- Chongyun Xing
- Wanling Xu
- Yifen Shi
- Bin Zhou
- Dijiong Wu
- Bin Liang
- Yuhong Zhou
- Shenmeng Gao
- Jianhua Feng
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Affiliations: Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China, Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China, Laboratory of Internal Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
Published online on: July 20, 2020 https://doi.org/10.3892/mmr.2020.11350
Pages: 2791-2800
Copyright: © Xing et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Philadelphia chromosome‑positive acute lymphoblastic leukemia (Ph+ ALL) is regarded as a prognostically unfavorable subgroup, as this ALL subgroup has an increased risk of relapse/refractory disease. CD9, which belongs to the tetraspanin membrane proteins, is implicated in several pathological processes, including tumor progression. However, the role of CD9 in the pathogenesis of Ph+ ALL and the potential benefit of applying CD9‑targeted RNA interference strategies for treatment of Ph+ ALL require further investigation. The aim of the present study was to determine the effects of CD9 on leukemic cell progression and the efficacy of therapeutic agents in Ph+ ALL cells, in addition to assessing the in vitro anti‑leukemia activity of CD9‑targeted RNA interference in Ph+ ALL cells. In the present study, a lentiviral short hairpin RNA (shRNA) expression vector targeting CD9 gene in Ph+ ALL SUP‑B15 cells was constructed. The present results demonstrated that treatment of SUP‑B15 cells with lentiviral‑mediated shRNA against CD9 decreased CD9 mRNA and protein expression compared with the shControl cells transduced with a blank vector. In addition, CD9 knockdown could suppress cell proliferation, adhesion, migration and invasion, and promote apoptosis and the efficacy of chemotherapeutic drugs (such as vincristine, daunorubicin, cyclophosphamide and dexamethasone) and the tyrosine kinase inhibitor imatinib in SUP‑B15 cells. Furthermore, CD9 knockdown suppressed cell proliferation and promoted apoptosis in SUP‑B15 cells via a p53‑dependent pathway. These findings suggested that gene silencing of CD9 using a shRNA‑expressing lentivirus vector may provide a promising treatment for Ph+ ALL.

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