Salidroside inhibits chronic myeloid leukemia cell proliferation and induces apoptosis by regulating the miR‑140‑5p/wnt5a/β‑catenin axis

Chen,Danjun; Luo,Cong

doi:10.3892/etm.2021.10684

Salidroside inhibits chronic myeloid leukemia cell proliferation and induces apoptosis by regulating the miR‑140‑5p/wnt5a/β‑catenin axis

Authors:
- Danjun Chen
- Cong Luo
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Affiliations: Department of Pharmacy, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China, Department of Hematology, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China
Published online on: September 2, 2021 https://doi.org/10.3892/etm.2021.10684
Article Number: 1249
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Salidroside, an active ingredient of Rhodiola rosea, exhibits antitumor effects in various types of cancer. However, the role of salidroside in chronic myeloid leukemia (CML) has not been elucidated. In the presents study, cell viability was assessed by CCK‑8 assay, while apoptosis was detected by flow cytometry. Reverse transcription‑quantitative PCR analysis was used to examine the expression levels of miR‑140‑5p in human CML cell lines. The expression levels of apoptosis and cell cycle‑associated proteins and of the wnt5a/β‑catenin signaling pathway were determined by western blot analysis. Bioinformatic analysis and luciferase reporter assays were employed to investigate the association between miR‑140‑5p and wnt5a. The results revealed that exposure of CML cells to salidroside (80 µM) inhibited cell proliferation and promoted apoptosis. In addition, salidroside treatment led to the upregulation of miR‑140‑5p expression. Furthermore, the inhibition of wnt5a/β‑catenin signaling pathway and the pro‑apoptotic effects induced by salidroside were attenuated by miR‑140‑5p silencing. Notably, wnt5a was revealed to be a direct target of miR‑140‑5p. The present findings indicated that salidroside exerted anti‑CML effects through regulating miR‑140‑5p by suppressing the wnt5a/β‑catenin signaling pathway. The present study provided evidence of the therapeutic role of salidroside in CML.

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1	Flis S and Chojnacki T: Chronic myelogenous leukemia, a still unsolved problem: Pitfalls and new therapeutic possibilities. Drug Des Devel Ther. 13:825–843. 2019.PubMed/NCBI View Article : Google Scholar
2	Gupta A and Khattry N: Current status of hematopoietic stem cell transplant in chronic myeloid leukemia. Indian J Med Paediatr Oncol. 35:207–210. 2014.PubMed/NCBI View Article : Google Scholar
3	Hino Y, Doki N, Yamamoto K, Senoo Y, Sasajima S, Sakaguchi M, Hattori K, Kaito S, Kurosawa S, Harada K, et al: Chronic myeloid leukemia relapsing ten years after allogenic bone marrow transplantation. Rinsho Ketsueki. 57:608–612. 2016.PubMed/NCBI View Article : Google Scholar : (In Japanese).
4	Jabbour E and Kantarjian H: Chronic myeloid leukemia: 2016 update on diagnosis, therapy, and monitoring. Am J Hematol. 91:252–265. 2016.PubMed/NCBI View Article : Google Scholar
5	Ross DM, Arthur C, Burbury K, Ko BS, Mills AK, Shortt J and Kostner K: Chronic myeloid leukaemia and tyrosine kinase inhibitor therapy: Assessment and management of cardiovascular risk factors. Intern Med J. 48 (Suppl 2):S5–S13. 2018.PubMed/NCBI View Article : Google Scholar
6	Li H, Liu L, Liu C, Zhuang J, Zhou C, Yang J, Gao C, Liu G, Lv Q and Sun C: Deciphering key pharmacological pathways of qingdai acting on chronic myeloid leukemia using a network pharmacology-based strategy. Med Sci Monit. 24:5668–5688. 2018.PubMed/NCBI View Article : Google Scholar
7	Zhang Y, Xiao Y, Dong Q, Ouyang W and Qin Q: Neferine in the lotus plumule potentiates the antitumor effect of imatinib in primary chronic myeloid leukemia cells in vitro. J Food Sci. 84:904–910. 2019.PubMed/NCBI View Article : Google Scholar
8	Lv C, Huang Y, Liu ZX, Yu D and Bai ZM: Salidroside reduces renal cell carcinoma proliferation by inhibiting JAK2/STAT3 signaling. Cancer Biomark. 17:41–47. 2016.PubMed/NCBI View Article : Google Scholar
9	Fan XJ, Wang Y, Wang L and Zhu M: Salidroside induces apoptosis and autophagy in human colorectal cancer cells through inhibition of PI3K/Akt/mTOR pathway. Oncol Rep. 36:3559–3567. 2016.PubMed/NCBI View Article : Google Scholar
10	Shang H, Wang S, Yao J, Guo C, Dong J and Liao L: Salidroside inhibits migration and invasion of poorly differentiated thyroid cancer cells. Thorac Cancer. 10:1469–1478. 2019.PubMed/NCBI View Article : Google Scholar
11	Qi Z, Tang T, Sheng L, Ma Y, Liu Y, Yan L, Qi S, Ling L and Zhang Y: Salidroside inhibits the proliferation and migration of gastric cancer cells via suppression of Src-associated signaling pathway activation and heat shock protein 70 expression. Mol Med Rep. 18:147–156. 2018.PubMed/NCBI View Article : Google Scholar
12	Kang DY, Sp N, Kim DH, Joung YH, Lee HG, Park YM and Yang YM: Salidroside inhibits migration, invasion and angiogenesis of MDAMB 231 TNBC cells by regulating EGFR/Jak2/STAT3 signaling via MMP2. Int J Oncol. 53:877–885. 2018.PubMed/NCBI View Article : Google Scholar
13	Yu G, Li N, Zhao Y, Wang W and Feng XL: Salidroside induces apoptosis in human ovarian cancer SKOV3 and A2780 cells through the p53 signaling pathway. Oncol Lett. 15:6513–6518. 2018.PubMed/NCBI View Article : Google Scholar
14	Ren M, Xu W and Xu T: Salidroside represses proliferation, migration and invasion of human lung cancer cells through AKT and MEK/ERK signal pathway. Artif Cells Nanomed Biotechnol. 47:1014–1021. 2019.PubMed/NCBI View Article : Google Scholar
15	Yang L, Yu Y, Zhang Q, Li X, Zhang C, Mao T, Liu S and Tian Z: Anti-gastric cancer effect of Salidroside through elevating miR-99a expression. Artif Cells Nanomed Biotechnol. 47:3500–3510. 2019.PubMed/NCBI View Article : Google Scholar
16	Li H, Huang D and Hang S: Salidroside inhibits the growth, migration and invasion of Wilms' tumor cells through down-regulation of miR-891b. Life Sci. 222:60–68. 2019.PubMed/NCBI View Article : Google Scholar
17	Wu Y, Li J, Chen S and Yu Z: The effects of miR-140-5p on the biological characteristics of ovarian cancer cells through the Wnt signaling pathway. Adv Clin Exp Med. 29:777–784. 2020.PubMed/NCBI View Article : Google Scholar
18	Fang Z, Yin S, Sun R, Zhang S, Fu M, Wu Y, Zhang T, Khaliq J and Li Y: miR-140-5p suppresses the proliferation, migration and invasion of gastric cancer by regulating YES1. Mol Cancer. 16(139)2017.PubMed/NCBI View Article : Google Scholar
19	Nie ZY, Liu XJ, Zhan Y, Liu MH, Zhang XY, Li ZY, Lu YQ, Luo JM and Yang L: miR-140-5p induces cell apoptosis and decreases Warburg effect in chronic myeloid leukemia by targeting SIX1. Biosci Rep. 39(BSR20190150)2019.PubMed/NCBI View Article : Google Scholar
20	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.PubMed/NCBI View Article : Google Scholar
21	Li JH, Liu S, Zhou H, Qu LH and Yang JH: StarBase v2.0: Decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res. 42:D92–D97. 2014.PubMed/NCBI View Article : Google Scholar
22	Jin YL, Zhang XM, Chen X, Liu J, Chang YY, Gao XY, Xue YM, Dong XS, Liu Y, Tian YY, et al: Salidroside induces apoptosis via ERK1/2 in human leukemia. K562 cells. 9:17588–17595. 2016.
23	Qie S and Diehl JA: Cyclin D1, cancer progression, and opportunities in cancer treatment. J Mol Med (Berl). 94:1313–1326. 2016.PubMed/NCBI View Article : Google Scholar
24	El-Deiry WS: p21(WAF1) mediates cell-cycle inhibition, relevant to cancer suppression and therapy. Cancer Res. 76:5189–5191. 2016.PubMed/NCBI View Article : Google Scholar
25	Litwinska Z and Machalinski B: miRNAs in chronic myeloid leukemia: Small molecules, essential function. Leuk Lymphoma. 58:1297–1305. 2017.PubMed/NCBI View Article : Google Scholar
26	Liao Y, Yin X, Deng Y and Peng X: MiR-140-5p suppresses retinoblastoma cell growth via inhibiting c-Met/AKT/mTOR pathway. Biosci Rep: Nov 30, 2018 (Epub ahead of print). doi: 10.1042/BSR20180776.
27	Jia Q, Sun H, Xiao F, Sai Y, Li Q, Zhang X, Yang S, Wang H, Wang H, Yang Y, et al: miR-17-92 promotes leukemogenesis in chronic myeloid leukemia via targeting A20 and activation of NF-κB signaling. Biochem Biophys Res Commun. 487:868–874. 2017.PubMed/NCBI View Article : Google Scholar
28	Cai H, Qin X and Yang C: Dehydrocostus lactone suppresses proliferation of human chronic myeloid leukemia cells through Bcr/Abl-JAK/STAT signaling pathways. J Cell Biochem. 118:3381–3390. 2017.PubMed/NCBI View Article : Google Scholar
29	Li L, Qi Y, Ma X, Xiong G, Wang L and Bao C: TRIM22 knockdown suppresses chronic myeloid leukemia via inhibiting PI3K/Akt/mTOR signaling pathway. Cell Biol Int. 42:1192–1199. 2018.PubMed/NCBI View Article : Google Scholar
30	Huang L, Huang Z, Lin W, Wang L, Zhu X, Chen X, Yang S and Lv C: Salidroside suppresses the growth and invasion of human osteosarcoma cell lines MG63 and U2OS in vitro by inhibiting the JAK2/STAT3 signaling pathway. Int J Oncol. 54:1969–1980. 2019.PubMed/NCBI View Article : Google Scholar
31	Zhao J, Du X, Wang M, Yang P and Zhang J: Salidroside mitigates hydrogen peroxide-induced injury by enhancement of microRNA-27a in human trabecular meshwork cells. Artif Cells Nanomed Biotechnol. 47:1758–1765. 2019.PubMed/NCBI View Article : Google Scholar
32	Cha Y, He Y, Ouyang K, Xiong H, Li J and Yuan X: MicroRNA-140-5p suppresses cell proliferation and invasion in gastric cancer by targeting WNT1 in the WNT/β-catenin signaling pathway. Oncol Lett. 16:6369–6376. 2018.PubMed/NCBI View Article : Google Scholar
33	Han XR, Wen X, Wang YJ, Wang S, Shen M, Zhang ZF, Fan SH, Shan Q, Wang L, Li MQ, et al: MicroRNA-140-5p elevates cerebral protection of dexmedetomidine against hypoxic-ischaemic brain damage via the Wnt/β-catenin signalling pathway. J Cell Mol Med. 22:3167–3182. 2018.PubMed/NCBI View Article : Google Scholar
34	Zhao G, Yin Y and Zhao B: miR-140-5p is negatively correlated with proliferation, invasion, and tumorigenesis in malignant melanoma by targeting SOX4 via the Wnt/β-catenin and NF-κB cascades. J Cell Physiol. 235:2161–2170. 2020.PubMed/NCBI View Article : Google Scholar