mRNA expression profile analysis reveals a C‑MYC/miR‑34a pathway involved in the apoptosis of diffuse large B‑cell lymphoma cells induced by Yiqichutan treatment

Zhai,Linzhu; Zhao,Yuanyuan; Liu,Zeyu; Wu,Jie; Lin,Lizhu

doi:10.3892/etm.2020.8940

mRNA expression profile analysis reveals a C‑MYC/miR‑34a pathway involved in the apoptosis of diffuse large B‑cell lymphoma cells induced by Yiqichutan treatment

Authors:
- Linzhu Zhai
- Yuanyuan Zhao
- Zeyu Liu
- Jie Wu
- Lizhu Lin
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Affiliations: Cancer Center, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China, Department of Medical Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China, Project Department, Forevergen Biosciences Co., Ltd., Guangzhou, Guangdong 510000, P.R. China
Published online on: June 25, 2020 https://doi.org/10.3892/etm.2020.8940
Pages: 2157-2165
Copyright: © Zhai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of adult non-Hodgkin's lymphoma (NHL). While DLBCL is sensitive to chemotherapy, a certain percentage of patients with DLBCL experience relapse. Previous studies have indicated that Yiqichutan treatment, which was developed to treat NHL, can inhibit DLBCL cell growth, but the mechanism is not fully understood. The present study identified 991 differentially expressed mRNAs, with 498 upregulated and 493 downregulated (P<0.05), in SUDHL‑6 cells exposed to Yiqichutan. The underlying pathways included the Jak/Stat and PI3K signaling pathways. In total, six representative mRNAs were selected for validation with reverse transcription‑quantitative PCR (RT‑qPCR), and a strong correlation was identified between the RT‑qPCR results and microarray data. Since the transcription factor C‑MYC is involved in both the Jak/Stat and PI3K signaling pathways, C‑MYC and its associated microRNA (miR) were selected for further analysis. It was found that knockdown of C‑MYC increased miR‑34a expression levels, inhibited forkhead box P1 (Foxp1) expression levels and promoted DLBCL cell apoptosis. In addition, the miR‑34a mimics further enhanced the role of C‑MYC knockdown. It was demonstrated that, the expression levels of apoptotic factors Bax and poly (ADP‑ribose) polymerase were significantly upregulated with C‑MYC knockdown and miR‑34a mimics in SUDHL‑6 cells, while the Bcl2 expression level was significantly reduced. Moreover, Yiqichutan treatment increased miR‑34a expression levels and induced apoptosis, as well as reducing Foxp1 expression level in SUDHL‑6 cells. Therefore, the present results suggested that Yiqichutan treatment affected DLBCL cells via several signaling pathways. Furthermore, Yiqichutan may inhibit the proliferation of DLBCL cells by blocking the C‑MYC/miR‑34a signaling pathway.

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