Puerarin inhibits hepatocellular carcinoma invasion and metastasis through miR-21-mediated PTEN/AKT signaling to suppress the epithelial-mesenchymal transition

Zhou, Yuan; Xue, Ruifeng; Wang, Jinglin; Ren, Haozhen

doi:10.1590/1414-431x20198882

Cited by 29 publications

(20 citation statements)

References 43 publications

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“…In particular, the downregulation of E-cadherin expression levels and upregulation of vimentin expression levels are the main characteristics of EMT ( 45 , 46 ). A previous study revealed that puerarin could inhibit hepatocellular carcinoma metastasis by upregulating the expression levels of epithelial markers and downregulating the expression levels of mesenchymal markers ( 47 ). Similarly, rosmarinic acid, an abundant phenolic ester found in Prunella vulgaris , could inhibit the EMT process by upregulating the expression levels of E-cadherin and downregulating the expression levels of vimentin, and then inhibited the development of colorectal cancer ( 24 ).…”

Section: Discussionmentioning

confidence: 99%

VSP‑17 suppresses the migration and invasion of triple‑negative breast cancer cells through inhibition of the EMT process via the PPARγ/AMPK signaling pathway

Yang

et al. 2020

Oncol Rep

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VSP-17, a novel peroxisome proliferator-activated receptor γ (PPARγ) agonist, has been previously demonstrated to suppress the metastasis of triple-negative breast cancer (TNBC) by upregulating the expression levels of E-cadherin, which is a key marker of epithelial-mesenchymal transition (EMT). However, the mechanism of action of VSP-17, in particular whether it may be associated with the EMT process, remains unknown. The present study investigated the ability of VSP-17 to inhibit the invasiveness and migratory ability of TNBC cell lines (MDA-MB-231 and MDA-MB-453) performed in in vitro experiments. including cell migration assay, cell invasion assay, cell transfection, RT-qPCR, western blot (WB) analysis and immunofluorescence. The present study aimed to ascertain whether and how the PPARγ/AMP-activated protein kinase (AMPK) signaling pathway serves a role in the inhibitory effects of VSP-17 on cell migration and invasion. The results revealed that both treatment with compound C (an AMPK inhibitor) and transfection with small interfering RNA (si)AMPK notably diminished the inhibitory effect of VSP-17 treatment on the migration and invasion of MDA-MB-231 and MDA-MB-453 cells, indicating that VSP-17 may, at least partly, exert its effects via AMPK. Furthermore, both compound C and siAMPK markedly diminished the VSP-17-induced downregulation of vimentin expression levels and upregulation of E-cadherin expression levels, further indicating that the VSP-17-induced inhibition of the EMT process may be dependent on AMPK. The combination of GW9662 (a PPARγ antagonist) or siPPARγ diminished the inhibitory effect of VSP-17 treatment on the migration and invasion of the TNBC cells, indicating that PPARγ may serve an important role in the VSP-17-induced inhibition of the migration and invasion of TNBC cells. In addition, both GW9662 and siPPARγ significantly reversed the VSP-17-induced downregulation of vimentin expression levels and upregulation of E-cadherin expression levels, implying that the VSP-17-induced inhibition of the EMT process may be dependent on PPARγ. VSP-17 treatment also upregulated the expression levels of p-AMPK, which could be reversed by either GW9662 or siPPARγ, indicating that the VSP-17-induced activation of the AMPK signaling pathway was PPARγ-dependent. In conclusion, the findings of the present study indicated that VSP-17 treatment may inhibit the migration and invasion of TNBC cells by suppressing the EMT process via the PPARγ/AMPK signaling pathway.

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Section: Discussionmentioning

confidence: 99%

VSP‑17 suppresses the migration and invasion of triple‑negative breast cancer cells through inhibition of the EMT process via the PPARγ/AMPK signaling pathway

Yang

et al. 2020

Oncol Rep

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“…This finding indicated that puerarin could upregulate PTEN expression by exerting a negative influence on miR-21, resulting in the inhibition of the EMT process in hepatocellular carcinoma cell lines. In addition, tumor sizes were smaller and there were fewer nodules in the livers of nude mice in the puerarin group [ 117 ]. Sevoflurane (SEV) could inhibit breast cancer migration, invasion, and the EMT process.…”

Section: Compounds Regulated Mirnas As Potential Therapeutics For Inhibiting Emtmentioning

confidence: 99%

MicroRNAs in Epithelial–Mesenchymal Transition Process of Cancer: Potential Targets for Chemotherapy

Peng

Fan

Sui

et al. 2021

IJMS

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In the last decades, a kind of small non-coding RNA molecules, called as microRNAs, has been applied as negative regulators in various types of cancer treatment through down-regulation of their targets. More recent studies exert that microRNAs play a critical role in the EMT process of cancer, promoting or inhibiting EMT progression. Interestingly, accumulating evidence suggests that pure compounds from natural plants could modulate deregulated microRNAs to inhibit EMT, resulting in the inhibition of cancer development. This small essay is on the purpose of demonstrating the significance and function of microRNAs in the EMT process as oncogenes and tumor suppressor genes according to studies mainly conducted in the last four years, providing evidence of efficient target therapy. The review also summarizes the drug candidates with the ability to restrain EMT in cancer through microRNA regulation.

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“…In human volunteers, increased plasma miR-21 levels have been reported 6 hours after milk consumption (231). Because human and bovine miR-21 sequences are identical (232), milk-derived exosomal miR-21 and HCC-induced exosomal miR-21 may synergistically promote hepatocancerogenesis (219)(220)(221)(222)(223)233).…”

Section: Mir-21mentioning

confidence: 99%

Dairy consumption and hepatocellular carcinoma risk

Melnik¹

2021

Ann Transl Med

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This review provides epidemiological and translational evidence for milk and dairy intake as critical risk factors in the pathogenesis of hepatocellular carcinoma (HCC). Large epidemiological studies in the United States and Europe identified total dairy, milk and butter intake with the exception of yogurt as independent risk factors of HCC. Enhanced activity of mechanistic target of rapamycin complex 1 (mTORC1) is a hallmark of HCC promoted by hepatitis B virus (HBV) and hepatitis C virus (HCV). mTORC1 is also activated by milk protein-induced synthesis of hepatic insulin-like growth factor 1 (IGF-1) and branched-chain amino acids (BCAAs), abundant constituents of milk proteins. Over the last decades, annual milk protein-derived BCAA intake increased 3 to 5 times in Western countries. In synergy with HBV-and HCV-induced secretion of hepatocyte-derived exosomes enriched in microRNA-21 (miR-21) and miR-155, exosomes of pasteurized milk as well deliver these oncogenic miRs to the human liver. Thus, milk exosomes operate in a comparable fashion to HBV-or HCV-induced exosomes. Milk-derived miRs synergistically enhance IGF-1-AKT-mTORC1 signaling and promote mTORC1-dependent translation, a meaningful mechanism during the postnatal growth phase, but a long-term adverse effect promoting the development of HCC. Both, dietary BCAA abundance combined with oncogenic milk exosome exposure persistently overstimulate hepatic mTORC1. Chronic alcohol consumption as well as type 2 diabetes mellitus (T2DM), two HCC-related conditions, increase BCAA plasma levels. In HCC, mTORC1 is further hyperactivated due to RAB1 mutations as well as impaired hepatic BCAA catabolism, a metabolic hallmark of T2DM. The potential HCC-preventive effect of yogurt may be caused by lactobacilli-mediated degradation of BCAAs, inhibition of branched-chain α-ketoacid dehydrogenase kinase via production of intestinal medium-chain fatty acids as well as degradation of milk exosomes including their oncogenic miRs. A restriction of total animal protein intake realized by a vegetable-based diet is recommended for the prevention of HCC.

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Puerarin inhibits hepatocellular carcinoma invasion and metastasis through miR-21-mediated PTEN/AKT signaling to suppress the epithelial-mesenchymal transition

Cited by 29 publications

References 43 publications

VSP‑17 suppresses the migration and invasion of triple‑negative breast cancer cells through inhibition of the EMT process via the PPARγ/AMPK signaling pathway

VSP‑17 suppresses the migration and invasion of triple‑negative breast cancer cells through inhibition of the EMT process via the PPARγ/AMPK signaling pathway

MicroRNAs in Epithelial–Mesenchymal Transition Process of Cancer: Potential Targets for Chemotherapy

Dairy consumption and hepatocellular carcinoma risk

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