Baicalin suppresses the progression of Type 2 diabetes-induced liver tumor through regulating METTL3/m6A/HKDC1 axis and downstream p-JAK2/STAT1/clevaged Capase3 pathway

Jiang, Hongpeng; Yao, Qianqian; An, Yongbo; Fan, Lei; Wang, Jing; Li, Huiying

doi:10.1016/j.phymed.2021.153823

Cited by 49 publications

(25 citation statements)

References 70 publications

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“…High glucose environment can induce hepatoma cells to up-regulate the expression of HKDC, which can promote the proliferation, invasion and metastasis of tumor cells by downregulating the HKDC/JAK2/STAT1/caspase-3 signaling pathway. Baicalin can reduce the m6A modification level of HKDC mRNA by inhibiting METTL3, which leads to the decrease of HKDC expression and the upregulation of HKDC/JAK2/STAT1/caspase-3 signaling pathway, and finally inhibits the invasion and metastasis of tumor cells ( Jiang et al, 2022 ). In addition, Baicalein inhibits pancreatic cancer cell proliferation and invasion by inhibiting NEDD9 and its downstream Akt and ERK signaling pathways ( Zhou et al, 2017 ).…”

Section: Part 3: the Anti-cancer Effect Of Nature Products By Regulat...mentioning

confidence: 99%

“…These natural products, including compounds with antibiotic, antifungal, immunosuppressant, and anticancer activity, are a rich source of anticancer agents and provide new and more effective anticancer agents for therapeutic use. However, there are few reports that natural products inhibit tumor genesis and development by regulating m6A RNA modification ( Qian et al, 2021b ; Feng et al, 2022 ; Jiang et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

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The Role of m6A RNA Methylation in Cancer: Implication for Nature Products Anti-Cancer Research

et al. 2022

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N6-methyladenosine (m6A) RNA methylation is identified as the most common, abundant and reversible RNA epigenetic modification in messenger RNA (mRNA) and non-coding RNA, especially within eukaryotic messenger RNAs (mRNAs), which post-transcriptionally directs many important processes of RNA. It has also been demonstrated that m6A modification plays a pivotal role in the occurrence and development of tumors by regulating RNA splicing, localization, translation, stabilization and decay. Growing number of studies have indicated that natural products have outstanding anti-cancer effects of their unique advantages of high efficiency and minimal side effects. However, at present, there are very few research articles to study and explore the relationship between natural products and m6A RNA modification in tumorigenesis. m6A is dynamically deposited, removed, and recognized by m6A methyltransferases (METTL3/14, METTL16, WTAP, RBM15/15B, VIRMA, CBLL1, and ZC3H13, called as “writers”), demethylases (FTO and ALKBH5, called as “erasers”), and m6A-specific binding proteins (YTHDF1/2/3, YTHDC1/2, IGH2BP1/2/3, hnRNPs, eIF3, and FMR1, called as “readers”), respectively. In this review, we summarize the biological function of m6A modification, the role of m6A and the related signaling pathway in cancer, such as AKT, NF-kB, MAPK, ERK, Wnt/β-catenin, STAT, p53, Notch signaling pathway, and so on. Furthermore, we reviewed the current research on nature products in anti-tumor, and further to get a better understanding of the anti-tumor mechanism, thus provide an implication for nature products with anti-cancer research by regulating m6A modification in the future.

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Section: Part 3: the Anti-cancer Effect Of Nature Products By Regulat...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Role of m6A RNA Methylation in Cancer: Implication for Nature Products Anti-Cancer Research

et al. 2022

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“…Baicalin suppressed type 2 diabetes and liver cancer development by reduction in the m6A level of HKDC1 by repressing the levels of m6A-related gene, METTL3. There was a significant reduction in the m6A (2854 site) levels of HKDC1 in METTL3-silenced cells [ 109 ].…”

Section: Animal Modelsmentioning

confidence: 99%

Regulation of Cell Signaling Pathways and Non-Coding RNAs by Baicalein in Different Cancers

Farooqi

Kapanova

Калмаханов

et al. 2022

IJMS

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Landmark discoveries in molecular oncology have provided a wide-angle overview of the heterogenous and therapeutically challenging nature of cancer. The power of modern ‘omics’ technologies has enabled researchers to deeply and comprehensively characterize molecular mechanisms underlying cellular functions. Interestingly, high-throughput technologies have opened new horizons for the design and scientific fool-proof evaluation of the pharmacological properties of targeted chemical compounds to tactfully control the activities of the oncogenic protein networks. Groundbreaking discoveries have galvanized the expansion of the repertoire of available pharmacopoeia to therapeutically target a myriad of deregulated oncogenic pathways. Natural product research has undergone substantial broadening, and many of the drugs which constitute the backbone of modern pharmaceuticals have been derived from the natural cornucopia. Baicalein has gradually gained attention because of its unique ability to target different oncogenic signal transduction cascades in various cancers. We have partitioned this review into different sub-sections to provide a broader snapshot of the oncogenic pathways regulated by baicalein. In this review, we summarize baicalein-mediated targeting of WNT/β-catenin, AKT/mTOR, JAK/STAT, MAPK, and NOTCH pathways. We also critically analyze how baicalein regulates non-coding RNAs (microRNAs and long non-coding RNAs) in different cancers. Finally, we conceptually interpret baicalein-mediated inhibition of primary and secondary growths in xenografted mice.

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“…Extracts from two herbs, including a natural extract from Gardenia jasminoides J. Ellis (GJ-4) ( Liu et al, 2021 ) and bisabolane-type sesquiterpenoids isolated from turmeric ( Ti et al, 2021 ), were mentioned here to antagonize Alzheimer’s disease (AD) and infection through inactivating STAT1. Correspondingly, about nine natural compounds and phytochemicals isolated from herbs and plants exhibited good performance in anti-cancer ( Liang et al, 2021a ; Jiang et al, 2022 ), treating allergic rhinitis ( Zhou et al, 2021 ), MS ( Du et al, 2021a ), nonalcoholic steatohepatitis ( Luo et al, 2021b ), anti-depression ( Zheng et al, 2021 ) and promoting skin-moisturizing activities ( Chen et al, 2021b ), acute lower respiratory tract infection ( Wang et al, 2020a ), renal inflammatory injury ( Hu et al, 2020 ), and ischemic cerebrovascular diseases ( Boriero et al, 2021 ) through influencing STAT1 signaling. Natural compounds’ combined utilization has been increasingly popular in recent years for their decrease of deficiencies and complementary advantages.…”

Section: Traditional Chinese Medicines or Herbs Or Natural Compounds ...mentioning

confidence: 99%

“…TS IIA and AS IV and TS IIA and Puerarin were presented here for their excellent performance in protecting against lumbar intervertebral disc degeneration ( Du et al, 2021b ) and idiopathic pulmonary fibrosis (IPF) ( Xue et al, 2021 ) through restricting STAT1 cascade via combined utilization. As mentioned above, potential candidates, including baicalin ( Jiang et al, 2022 ), dihydroartemisinin ( Du et al, 2021a ), kahweol ( Chen et al, 2021b ), and Yu-Ping-Feng decoction ( Zhou et al, 2021 ), exerted their anti-cancer and anti-infection properties through upregulating cell apoptosis and reinforcing immune system via activating STAT1 signaling, which caused high levels of apoptotic proteins, that is, caspases and enhanced the expression of immune cells, such as T cells and B cells. Conversely, compounds effectively treated allergic rhinitis ( Zhou et al, 2021 ) and influenza ( Ti et al, 2021 ) through inhibiting STAT1 signaling, reducing the expression of inflammatory mediators, and regulating cell differentiation.…”

Section: Traditional Chinese Medicines or Herbs Or Natural Compounds ...mentioning

confidence: 99%

Perspectives of herbs and their natural compounds, and herb formulas on treating diverse diseases through regulating complicated JAK/STAT signaling

et al. 2022

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JAK/STAT signaling pathways are closely associated with multiple biological processes involved in cell proliferation, apoptosis, inflammation, differentiation, immune response, and epigenetics. Abnormal activation of the STAT pathway can contribute to disease progressions under various conditions. Moreover, tofacitinib and baricitinib as the JAK/STAT inhibitors have been recently approved by the FDA for rheumatology disease treatment. Therefore, influences on the STAT signaling pathway have potential and perspective approaches for diverse diseases. Chinese herbs in traditional Chinese medicine (TCM), which are widespread throughout China, are the gold resources of China and have been extensively used for treating multiple diseases for thousands of years. However, Chinese herbs and herb formulas are characterized by complicated components, resulting in various targets and pathways in treating diseases, which limits their approval and applications. With the development of chemistry and pharmacology, active ingredients of TCM and herbs and underlying mechanisms have been further identified and confirmed by pharmacists and chemists, which improved, to some extent, awkward limitations, approval, and applications regarding TCM and herbs. In this review, we summarized various herbs, herb formulas, natural compounds, and phytochemicals isolated from herbs that have the potential for regulating multiple biological processes via modulation of the JAK/STAT signaling pathway based on the published work. Our study will provide support for revealing TCM, their active compounds that treat diseases, and the underlying mechanism, further improving the rapid spread of TCM to the world.

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Baicalin suppresses the progression of Type 2 diabetes-induced liver tumor through regulating METTL3/m6A/HKDC1 axis and downstream p-JAK2/STAT1/clevaged Capase3 pathway

Cited by 49 publications

References 70 publications

The Role of m6A RNA Methylation in Cancer: Implication for Nature Products Anti-Cancer Research

The Role of m6A RNA Methylation in Cancer: Implication for Nature Products Anti-Cancer Research

Regulation of Cell Signaling Pathways and Non-Coding RNAs by Baicalein in Different Cancers

Perspectives of herbs and their natural compounds, and herb formulas on treating diverse diseases through regulating complicated JAK/STAT signaling

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