Melatonin Inhibits the Progression of Hepatocellular Carcinoma through MicroRNA Let7i-3p Mediated RAF1 Reduction

Wang, Tong Hong; Li, Wan-Syuan; Yeh, Chau‐Ting; Lian, Jang-Hau; Chang, Junn-Liang; Chen, Chi-Yuan

doi:10.3390/ijms19092687

Cited by 34 publications

(22 citation statements)

References 51 publications

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“…Additionally, not only lncRNAs but also some micro-RNAs have been implicated in the anti-invasive and antimetastatic activities of melatonin in HCC. In the same way, also in HepG2 and HuH7 cell lines, administration of 1 and 2 mM melatonin induced the miRNA let7i-p activation, which in turn downregulated the ras activated factor 1 (RAF-1) proto-oncogene, impaired HCC cell migration [ 53 ].…”

Section: Resultsmentioning

confidence: 99%

Melatonin as an Antitumor Agent against Liver Cancer: An Updated Systematic Review

et al. 2021

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Melatonin (N-acetyl-5-methoxytryptamine) is an indoleamine with antioxidant, chronobiotic and anti-inflammatory properties; reduced levels of this hormone are associated with higher risk of cancer. Several beneficial effects of melatonin have been described in a broad number of tumors, including liver cancers. In this work we systematically reviewed the publications of the last 15 years that assessed the underlying mechanisms of melatonin activities against liver cancers, and its role as coadjuvant in the treatment of these tumors. Literature research was performed employing PubMed, Scopus and Web of Science (WOS) databases and, after screening, 51 articles were included. Results from the selected studies denoted the useful actions of melatonin in preventing carcinogenesis and as a promising treatment option for the primary liver tumors hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), either alone or in combination with other compounds. Different processes were modulated by the indole, such as inhibition of oxidative stress, proliferation, angiogenesis and invasion, promotion of immune system response, cell cycle arrest and apoptosis, as well as recovery of circadian rhythms and autophagy modulation. Taken together, the present systematic review highlights the evidence that document the potential role of melatonin in improving the landscape of liver tumor treatment.

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Section: Resultsmentioning

confidence: 99%

Melatonin as an Antitumor Agent against Liver Cancer: An Updated Systematic Review

et al. 2021

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“…More recent studies have demonstrated that melatonin may also modulate the expression of non-coding microRNAs (or, miRNA), which modulate many aspects of tumor phenotypes in breast, liver and gastric cancers [21,22,23]. In fact, melatonin may modulate expression of specific microRNAs that function across multiple tumor types, such as miR-155, miR-133a and miR-21 [24,25,26].…”

Section: Introductionmentioning

confidence: 99%

Differential MicroRNA Expression of miR-21 and miR-155 within Oral Cancer Extracellular Vesicles in Response to Melatonin

et al. 2019

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Objective: Extracellular vesicles derived from oral cancer cells, which include Exosomes and Oncosomes, are membranous vesicles secreted into the surrounding extracellular environment. These extracellular vesicles can regulate and modulate oral squamous cell carcinoma (OSCC) progression through the horizontal transfer of bioactive molecules including proteins, lipids and microRNA (miRNA). The primary objective of this study was to examine the potential to isolate and evaluate extracellular vesicles (including exosomes) from various oral cancer cell lines and to explore potential differences in miRNA content. Methods: The OSCC cell lines SCC9, SCC25 and CAL27 were cultured in DMEM containing 10% exosome-free fetal bovine serum. Cell-culture conditioned media was collected for exosome and extracellular vesicle isolation after 72 h. Isolation was completed using the Total Exosome Isolation reagent (Invitrogen) and extracellular vesicle RNA was purified using the Total Exosome RNA isolation kit (Invitrogen). Extracellular vesicle miRNA content was evaluated using primers specific for miR-16, -21, -133a and -155. Results: Extracellular vesicles were successfully isolated from all three OSCC cell lines and total extracellular vesicle RNA was isolated. Molecular screening using primers specific for several miRNA revealed differential baseline expression among the different cell lines. The addition of melatonin significantly reduced the expression of miR-155 in all of the OSCC extracellular vesicles. However, miR-21 was significantly increased in each of the three OSCC isolates. No significant changes in miR-133a expression were observed under melatonin administration. Conclusions: Although many studies have documented changes in gene expression among various cancers under melatonin administration, few studies have evaluated these effects on microRNAs. These results may be among the first to evaluate the effects of melatonin on microRNA expression in oral cancers, which suggests the differential modulation of specific microRNAs, such as miR-21, miR-133a and miR-155, may be of significant importance when evaluating the mechanisms and pathways involved in melatonin-associated anti-tumor effects.

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“…In addition, let‐7i‐3p was found to be related to hepatocellular carcinoma and hepatoblastoma (HBL). RAF1 reduction mediated by let‐7i‐3p plays a role in melatonin inhibition of hepatocellular carcinoma . Indersie et al reported that let‐71‐3p, miR‐449b‐3p, and miR‐885‐5p were decreased in tumors compared to normal livers, and that these miRNAs inhibited HBL cell grow and Wnt signaling activity in vitro, partly through beta‐catenin downregulation .…”

Section: Discussionmentioning

confidence: 99%

Serum exosomal microRNA let‐7i‐3p as candidate diagnostic biomarker for Kawasaki disease patients with coronary artery aneurysm

et al. 2019

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Kawasaki disease (KD) is a systemic vasculitis syndrome that leads to coronary artery aneurysm (CAA). While echocardiography is the most important imaging modality for coronary artery assessment, a specific diagnostic biomarker complementary for CAA has not been reported. We aimed to analyze the profiles of exosomal miRNAs extracted from the serum of KD patients and controls to identify candidate biomarkers for CAA. Serum samples from 39 healthy children, 42 CAA patients, 38 coronary artery dilatation (CAD) patients and 45 virus‐infected patients including 24 EBV patients and 21 ADV patients were randomly selected. Next generation sequencing was used to analyze serum exosomal miRNA to detect differentially expressed miRNAs. Biomarker candidates were validated by qRT‐PCR. One hundred (and) ninety‐six differentially expressed miRNAs (DEMs) were detected in CAA patients and healthy children. There were 70 DEMs and 140 DEMs in CAA patients versus CAD patients, and in CAA patients versus virus‐infected patients, respectively. We selected the three most upregulated (let‐7i‐3p, miR‐17‐3p, and miR‐210‐5p) and the three most downregulated miRNAs (miR‐6743‐5p, miR‐1246, and miR‐6834‐5p) in the DEMs, which were expressed differentially in CAA patients versus healthy children, and in CAA patients versus virus‐infected patients, not in virus‐infected patients versus healthy children, as biomarker candidates. Excluded DEMs of CAD and virus‐infected patients, let‐7i‐3p was detected by sequence data analysis as a biomarker candidate for CAA patients, and then validated by qRT‐PCR in a larger set of clinical samples. As a biomarker candidate, let‐7i‐3p provides an additional means of diagnosing CAA patients. Additionally, miRNA biomarkers complement ultrasonic imaging, allowing for greater diagnostic precision. © 2019 IUBMB Life, 2019

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Melatonin Inhibits the Progression of Hepatocellular Carcinoma through MicroRNA Let7i-3p Mediated RAF1 Reduction

Cited by 34 publications

References 51 publications

Melatonin as an Antitumor Agent against Liver Cancer: An Updated Systematic Review

Melatonin as an Antitumor Agent against Liver Cancer: An Updated Systematic Review

Differential MicroRNA Expression of miR-21 and miR-155 within Oral Cancer Extracellular Vesicles in Response to Melatonin

Serum exosomal microRNA let‐7i‐3p as candidate diagnostic biomarker for Kawasaki disease patients with coronary artery aneurysm

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