echemi logo
Product
  • Product
  • Supplier
  • Inquiry
    Home > Active Ingredient News > Antitumor Therapy > STTT Fuzhou University Jia Li and other teams found potential therapeutic targets for melanoma

    STTT Fuzhou University Jia Li and other teams found potential therapeutic targets for melanoma

    • Last Update: 2021-10-21
    • Source: Internet
    • Author: User
    Search more information of high quality chemicals, good prices and reliable suppliers, visit www.echemi.com
    Editor’s note iNature is China’s largest academic official account.
    It is jointly created by the doctoral team of Tsinghua University, Harvard University, Chinese Academy of Sciences and other units.
    The iNature Talent Official Account is now launched, focusing on talent recruitment, academic progress, scientific research information, interested parties can Long press or scan the QR code below to follow us
    .

    iNature metastasis is the cause of most deaths in cancer patients, and the mechanism is still poorly understood
    .

    There is an urgent need to decipher the regulatory network behind cancer cell metastasis
    .

    According to reports, nucleolar protein 7 (NOL7) can be used as a tumor suppressor for cervical cancer
    .

    On October 13, 2021, Fuzhou University Jia Li and Russian Far Eastern Federal University Vladimir L.
    Katanaev jointly published a research paper entitled "NOL7 facilitates melanoma progression and metastasis" in Signal Transduction and Targeted Therapy (IF=18.
    19).
    Studies have shown that NOL7 has a cancer-promoting effect on the progression and metastasis of melanoma
    .

    From a functional point of view, NOL7 is conducive to cell survival, and promotes tumor growth and metastasis of melanoma by promoting cell proliferation, cell cycle progression and invasiveness, and acquiring chemical and anoikis resistance
    .

    From a mechanism point of view, NOL7 appears as a new participant in the HIF-1α/NOL7/HRas/PI3K/AKT/ERK axis, and ultimately activates cell cycle, cell apoptosis and EMT regulators to exert its carcinogenic function
    .

    Therefore, the study identified NOL7 as a multifunctional regulator of malignant activity, and suggested that it be used as a new biomarker for melanoma progression and a potential drug target for future treatment
    .

    Metastasis is the cause of most deaths in cancer patients, and the mechanism is still poorly understood
    .

    There is an urgent need to decipher the regulatory network behind cancer cell metastasis
    .

    According to reports, nucleolar protein 7 (NOL7) can be used as a tumor suppressor for cervical cancer
    .

    This study revealed the novel tumor-promoting ability of NOL7 in melanoma
    .

    The study first detected that the expression of NOL7 in metastatic melanoma compared with its expression in the primary site was up-regulated by isobaric markers for relative and absolute quantitative proteomics screening, and by analyzing NOL7 protein and messenger RNA (MRNA) levels further confirmed this finding
    .

    Importantly, NOL7 expression increases as the disease progresses from benign moles to primary melanoma and further to metastatic melanoma
    .

    Previous studies have shown that melanoma is usually associated with the amplification of chromosomal region 6p, especially 6p21-23 where the NOL7 gene is located, and that this region often suffers from loss of heterozygosity in cervical cancer
    .

    Therefore, it can be predicted that NOL7 exhibits different expression patterns and plays different roles in melanoma and cervical cancer
    .

    In order to study the role of NOL7 in different melanoma activities, this study suppressed NOL7 expression through specific small interfering RNA and CRISPR/Cas9 gene editing system in the melanoma cell lines B16F10 and A375
    .

    In this way, the study observed that NOL7 knockdown/knockout significantly reduced the proliferation capacity
    .

    These effects of NOL7 knockdown are associated with decreased levels of cell cycle regulators CDK2, cyclin A, and cyclin E, as well as increased levels of cell cycle progression inhibitors p21 and p27
    .

    Then began to study the potential role of NOL7 in melanoma cell apoptosis
    .

    The apoptosis assay based on annexin V-FITC/PI and JC-1 staining showed that NOL7 knockdown/knockout cells have a higher apoptotic index
    .

    In addition, compared with control melanoma cells, the MTT assay showed that NOL7 knockdown cells were more sensitive to paclitaxel
    .

    Taken together, these results indicate the importance of melanoma NOL7 in regulating apoptosis and cell adaptation, and protecting against stress conditions such as chemotherapy or anoikis
    .

    Next, begin to study the function of NOL7 in metastasis
    .

    After NOL7 knockdown, the motility, adhesion, migration and invasiveness of B16F10 and A375 cells were significantly reduced
    .

    In addition, NOL7 depletion increased the expression of epithelial marker E-cadherin and decreased the levels of mesenchymal markers N-cadherin, mmp9, and vimentin in B16F10 and A375 cells
    .

    Therefore, these findings prove that NOL7 plays a vital role in the aggressive behavior of melanoma in vitro
    .

    To further study the role of NOL7 in the growth and metastasis of melanoma in vivo, this study uses A375-sgNOL7 cells and control cells to establish subcutaneous tumor mouse models and experimental metastasis models
    .

    The study found that NOL7 knockout significantly reduced the growth of subcutaneous tumors and lung metastatic nodules in nude mice
    .

    In addition, it was observed that NOL7 correlates with the overall survival rate of mice in the experimental metastasis model
    .

    The pattern diagram of the article (picture from Signal Transduction and Targeted Therapy) uses Western blotting to test the expression of hypoxia-inducible factor-1α (HIF-1α) and NOL7 in A375 cells exposed to hypoxic conditions (1% O2) for different durations
    .

    The study found that, like HIF-1α, NOL7 expression accumulates during hypoxia
    .

    After NOL7 was knocked out in A375 cells, hypoxia still resulted in increased HIF-1α expression, which was further consistent with the hypoxia-HIF-1α-NOL7 axis
    .

    In order to provide direct evidence to support this axis, the study used dual luciferase reporter gene assays to further determine the transcriptional activity of HIF-1α on the NOL7 promoter sequence
    .

    In fact, HIF-1α can induce NOL7 expression by promoting NOL7 transcription
    .

    In addition, culturing A375 cells under hypoxic conditions promoted the conversion of non-polar epithelial phenotype to polar mesenchymal phenotype, and changed the expression of epithelial-mesenchymal transition (EMT) related proteins (E-cadherin) , N-cadherin, vimentin and fibronectin)
    .

    However, NOL7 depletion reversed hypoxia-induced EMT
    .

    After hypoxia treatment, the invasion, migration and chemoresistance of A375 cells to paclitaxel were significantly enhanced, while NOL7 knockout impaired the increased cell invasion and migration characteristics and chemoresistance
    .

    Therefore, NOL7 is induced by HIF-1α under hypoxic conditions and is required for HIF-1α-induced EMT, invasiveness, and chemoresistance
    .

    It is hypothesized that NOL7 can affect the translation efficiency of HRas mRNA, thereby regulating the level of HRas protein and the PI3K/AKT/ERK signaling pathway
    .

    In fact, the study found that NOL7 consumption significantly reduced HRas protein levels in B16F10 and A375 melanoma cells, while HRas transcription levels were not affected
    .

    In summary, this study shows that NOL7 plays a cancer-promoting effect on the progression and metastasis of melanoma
    .

    From a functional point of view, NOL7 is conducive to cell survival, and promotes tumor growth and metastasis of melanoma by promoting cell proliferation, cell cycle progression and invasiveness, and acquiring chemical and anoikis resistance
    .

    From a mechanism point of view, NOL7 appears as a new participant in the HIF-1α/NOL7/HRas/PI3K/AKT/ERK axis, and ultimately activates cell cycle, cell apoptosis and EMT regulators to exert its carcinogenic function
    .

    Therefore, the study identified NOL7 as a multifunctional regulator of malignant activity, and suggested that it be used as a new biomarker for melanoma progression and a potential drug target for future treatment
    .

    Reference message: https://
    This article is an English version of an article which is originally in the Chinese language on echemi.com and is provided for information purposes only. This website makes no representation or warranty of any kind, either expressed or implied, as to the accuracy, completeness ownership or reliability of the article or any translations thereof. If you have any concerns or complaints relating to the article, please send an email, providing a detailed description of the concern or complaint, to service@echemi.com. A staff member will contact you within 5 working days. Once verified, infringing content will be removed immediately.

    Contact Us

    The source of this page with content of products and services is from Internet, which doesn't represent ECHEMI's opinion. If you have any queries, please write to service@echemi.com. It will be replied within 5 days.

    Moreover, if you find any instances of plagiarism from the page, please send email to service@echemi.com with relevant evidence.