MicroRNA‐324‐5p regulates stemness, pathogenesis and sensitivity to bortezomib in multiple myeloma cells by targeting hedgehog signaling

Tang, Bo; Xu, Aihua; Xu, Jian; Huang, Huapin; Chen, Lei; Su, Yan; Zhang, Lannan; Li, Junying; Fan, Fengjuan; Deng, Jun; Tang, Liang; Sun, Chaoyang; Hu, Yu

doi:10.1002/ijc.31041

Cited by 67 publications

(43 citation statements)

References 43 publications

(58 reference statements)

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“…Here we identified PKM2-targeting miR-324-5p as another target microRNA sponged by H19, and H19 therefore was a pro-Warburg lncRNA while miR-324-5p was an anti-Warburg microRNA. miR-324-5p has been reported as both oncomiR and tumor repressor in cancers because it inhibited cell growth and invasion in multiple myeloma and hepatocellular cancer [30], while promoted proliferation, migration and invasion of papillary thyroid microcarcinoma cells and breast cancer cells [31,32]. But most published results were from in vitro data.…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside 20(S)-Rg3 Prevents PKM2-Targeting miR-324-5p from H19 Sponging to Antagonize the Warburg Effect in Ovarian Cancer Cells

Zheng

Zhou

Chen

et al. 2018

Cell Physiol Biochem

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Background/Aims: The Warburg effect is one of the main metabolic features for cancers, with long non-coding RNA (lncRNA) being involved as a class of crucial regulators. Our previous studies have shown that ginsenoside 20(S)-Rg3, an active saponin monomer extracted from red ginseng, inhibits the Warburg effect in ovarian cancer cells. However, the detailed lncRNA regulatory network modulated by 20(S)-Rg3 to prevent the Warburg effect in ovarian cancer cells has not been explored. Methods: High-throughput sequencing was used to screen out the differentially expressed lncRNAs between 20(S)-Rg3-treated and non-treated SKOV3 cells. The levels of lncRNA H19 and miR-324-5p were manipulated in SKOV3 and A2780, and the glucose consumption, lactate production and PKM2 protein level were detected. Dual-luciferase reporter assay and RIP were utilized to verify the direct binding of H19 to miR-324-5p and miR-324-5p to PKM2. Cell proliferation was examined by CCK8 and colony formation assay. Nude mice subcutaneous xenograft tumor models were established to evaluate the impact of miR-324-5p on tumor growth in vivo. Results: 20(S)-Rg3 downregulated 67 lncRNAs, and H19 was one of the most decreased lncRNAs. Suppression of H19 by siRNA transfection reduced glucose consumption, lactate production and PKM2 expression in ovarian cancer cells, while H19 overexpression in 20(S)-Rg3-treated ovarian cancer cells enhanced glucose consumption, lactate production and PKM2 expression. Dual-luciferase reporter assay and RIP results showed that H19 directly bound to miR-324-5p. Dual-luciferase reporter assay showed that miR-324-5p directly targeted PKM2, and miR-324-5p negatively regulated glucose consumption and lactate production in ovarian cancer cells. miR-324-5p overexpression inhibited cell proliferation in vitro and in vivo. Conclusion: Our study revealed that 20(S)-Rg3 blocked the competitive inhibition of H19 on miR-324-5p, which enhanced the suppression of miR-324-5p on PKM2 and therefore inhibited the Warburg effect and repressed tumorigenesis. In a word, 20(S)-Rg3 inhibited the Warburg effect in ovarian cancer cells via H19/miR-324-5p/PKM2 pathway.

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Section: Discussionmentioning

confidence: 99%

Ginsenoside 20(S)-Rg3 Prevents PKM2-Targeting miR-324-5p from H19 Sponging to Antagonize the Warburg Effect in Ovarian Cancer Cells

Zheng

Zhou

Chen

et al. 2018

Cell Physiol Biochem

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“…Moreover, miR‐324‐5p has also been proved to inhibit cancer cell invasion and migration in breast cancer and hepatocellular carcinoma . In multiple myeloma (MM), miR‐324‐5p was decreased, and overexpressed miR‐324‐5p significantly reduced cancer cell growth and increased the sensitivity of MM cells to bortezomib in vit r o . The functional role of miR‐324‐5p in gastric cancer was first proved in this study.…”

Section: Discussionmentioning

confidence: 99%

MiR-324-5p reduces viability and induces apoptosis in gastric cancer cells through modulating TSPAN8

Lin

Zhou

Zhang

et al. 2018

Journal of Pharmacy and Pharmacology

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“…For example, miR-324-5p significantly decreases SMO and Gli1 in myeloma stem cells. 270 Mir-326 directly downregulates SMO and Gli2 in medulloblastoma stem cells. 271 MiR-326 downregulates SMO in glioma stem cells.…”

Section: Major Signaling Pathways In Cscsmentioning

confidence: 99%

Targeting cancer stem cell pathways for cancer therapy

Yang

Shi

Zhao

et al. 2020

Sig Transduct Target Ther

1,318

998

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Since cancer stem cells (CSCs) were first identified in leukemia in 1994, they have been considered promising therapeutic targets for cancer therapy. These cells have self-renewal capacity and differentiation potential and contribute to multiple tumor malignancies, such as recurrence, metastasis, heterogeneity, multidrug resistance, and radiation resistance. The biological activities of CSCs are regulated by several pluripotent transcription factors, such as OCT4, Sox2, Nanog, KLF4, and MYC. In addition, many intracellular signaling pathways, such as Wnt, NF-κB (nuclear factor-κB), Notch, Hedgehog, JAK-STAT (Janus kinase/signal transducers and activators of transcription), PI3K/AKT/mTOR (phosphoinositide 3-kinase/AKT/mammalian target of rapamycin), TGF (transforming growth factor)/SMAD, and PPAR (peroxisome proliferator-activated receptor), as well as extracellular factors, such as vascular niches, hypoxia, tumor-associated macrophages, cancer-associated fibroblasts, cancer-associated mesenchymal stem cells, extracellular matrix, and exosomes, have been shown to be very important regulators of CSCs. Molecules, vaccines, antibodies, and CAR-T (chimeric antigen receptor T cell) cells have been developed to specifically target CSCs, and some of these factors are already undergoing clinical trials. This review summarizes the characterization and identification of CSCs, depicts major factors and pathways that regulate CSC development, and discusses potential targeted therapy for CSCs.Signal Transduction and Targeted Therapy (2020) 5:8; https://doi.

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MicroRNA‐324‐5p regulates stemness, pathogenesis and sensitivity to bortezomib in multiple myeloma cells by targeting hedgehog signaling

Cited by 67 publications

References 43 publications

Ginsenoside 20(S)-Rg3 Prevents PKM2-Targeting miR-324-5p from H19 Sponging to Antagonize the Warburg Effect in Ovarian Cancer Cells

Ginsenoside 20(S)-Rg3 Prevents PKM2-Targeting miR-324-5p from H19 Sponging to Antagonize the Warburg Effect in Ovarian Cancer Cells

MiR-324-5p reduces viability and induces apoptosis in gastric cancer cells through modulating TSPAN8

Targeting cancer stem cell pathways for cancer therapy

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