Irisin stimulates cell proliferation and invasion by targeting the PI3K/AKT pathway in human hepatocellular carcinoma

Shi, Guangjun; Tang, Nan; Qiu, Jiantao; Zhang, Deguo; Huang, Fei; Cheng, Yayu; Ding, Kun; Li, Weisheng; Zhang, Ping; Tan, Xueying

doi:10.1016/j.bbrc.2017.08.148

Cited by 73 publications

(85 citation statements)

References 30 publications

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“…More interestingly, FNDC5 and MYCN have been specifically associated with liver cancer progression. Shi et al reported that FNDC5, a myokine also known as irisin, stimulated HepG2 cell proliferation and invasion by activating the PI3K/AKT pathway . Kojima’s group reported that MYCN levels could serve as a relevant prognostic factor for HCC given the strong association between MYCN gene expression and liver CSC markers …”

Section: Resultsmentioning

confidence: 99%

MicroRNA‐493‐5p‐mediated repression of the MYCN oncogene inhibits hepatic cancer cell growth and invasion

Yasukawa

Liew

Hagiwara³

et al. 2020

Cancer Science

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Primary hepatic tumors mainly include hepatocellular carcinoma (HCC), which is one of the most frequent causes of cancer‐related deaths worldwide. Thus far, HCC prognosis has remained extremely poor given the lack of effective treatments. Numerous studies have described the roles played by microRNAs (miRNAs) in cancer progression and the potential of these small noncoding RNAs for diagnostic or therapeutic applications. The current consensus supports the idea that direct repression of a wide range of oncogenes by a single key miRNA could critically affect the malignant properties of cancer cells in a synergistic manner. In this study, we aimed to investigate the oncogenes controlled by miR‐493‐5p, a major tumor suppressor miRNA that inactivates miR‐483‐3p oncomir in hepatic cancer cells. Using global gene expression analysis, we highlighted a set of candidate genes potentially regulated by miR‐493‐5p. In particular, the canonical MYCN protooncogene (MYCN) appeared to be an attractive target of miR‐493‐5p given its significant inhibition through 3′‐UTR targeting in miR‐493‐5p‐rescued HCC cells. We showed that MYCN was overexpressed in liver cancer cell lines and clinical samples from HCC patients. Notably, MYCN expression levels were inversely correlated with miR‐493‐5p in tumor tissues. We confirmed that MYCN knockdown mimicked the anticancer effect of miR‐493‐5p by inhibiting HCC cell growth and invasion, whereas MYCN rescue hindered miR‐493‐5p activity. In summary, miR‐493‐5p is a pivotal miRNA that modulates various oncogenes after its reexpression in liver cancer cells, suggesting that tumor suppressor miRNAs with a large spectrum of action could provide valuable tools for miRNA replacement therapies.

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Section: Resultsmentioning

confidence: 99%

MicroRNA‐493‐5p‐mediated repression of the MYCN oncogene inhibits hepatic cancer cell growth and invasion

Yasukawa

Liew

Hagiwara³

et al. 2020

Cancer Science

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“…However, more recent studies revealed additional vital roles for Fndc5/irisin in other tissues [36,87,88]. Recent studies have revealed that Irisin has anti-cancer, -depression, -hypertension and -cardiac hypertrophy properties [57,62,68,[81][82][83].…”

Section: Discussionmentioning

confidence: 99%

“…Specifically, irisin inhibited EMT and reduced the invasion of lung cancer cells via the PI3K/AKT/Snail pathway [56]. Conversely however, increased irisin levels may have protective roles in liver cancer cells through partial activation of the PI3K/ AKT pathway, which may facilitate liver cancer progression and decrease the sensitivity to chemotherapy [57] ( Table 1).…”

Section: Irisin Exerts Its Anti-metastatic Effects Via the Pi3k/akt Pmentioning

confidence: 99%

New insights into the cellular activities of Fndc5/Irisin and its signaling pathways

et al. 2020

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Fndc5, a well-defined myokine and also identified as an adipokine, has a critical role in modulation of metabolism and protection against obesity. These important functions are mediated by irisin, a secretory peptide produced from proteolytic processing of Fndc5. The other beneficial physiological effects of irisin are alleviation of oxidative stress, neuroprotective effects, and anti-inflammatory properties and associated anti-metastatic effects. Fndc5/irisin exerts its biological effects through several intracellular signaling pathways. The major signaling pathway is thought to be MAPK signaling pathways which are involved in neural differentiation, browning of white adipocytes, as well as osteoblast proliferation and differentiation. Other essential functions of Fndc5/irisin are mediated through additional pathways including AMPK pathway, PI3K/AKT, and STAT3/Snail. Thorough understanding of the mechanisms of irisin actions are essential in order to develop Fndc5/irisin for therapeutic purposes. In the present review, we focus on the current knowledge of the signaling pathways that elicit irisin actions.

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“…Moon et al, (2014) reported that irisin has no significant effect on the malignancy potential and cell proliferation of colon and endometrial cancer cells. In another similar study, Shi et al, (2017) reported that irisin significantly increased cell proliferation, invasion and migration in liver cancer. They also showed that irisin decreased the sensitivity of doxorubicin to liver cancer cells.…”

Section: Relationship Between Prostate Volume and Irisin And Roc Anamentioning

confidence: 87%

Can the Irisin be a Biomarker for Prostate Cancer? A Case Control Study

Aslan

Hakan

Eryılmaz

et al. 2020

Asian Pac J Cancer Prev

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Aim: There is much evidence of an association between cancer and irisin that is an adipokine. This study researched on the relationship between prostate cancer (PCa) and irisin levels, and whether irisin can be used as a biomarker in the diagnosis of PCa. Materials and Methods: For the study groups, 50 primary PCa patients and 30 healthy male subjects were included in the PCa and healthy control groups, respectively. All volunteers in the healthy control group were screened for prostate cancer and other malignancies and chronic diseases. Volunteers who were determine to be completely healthy were included for healthy control group. In the serum samples of the subjects were measured free PSA, total PSA and irisin levels. Irisin levels were compared separately in terms of the Gleason scores and T stage. In addition to intergroup comparisons, the ROC curve for the irisin was plotted and power analysis was performed. Results: Free and total PSA levels in the PCa group were significantly higher compared to the healthy control group (p<0.05). In addition, irisin levels in the PCa group were significantly lower than in the healthy control group (p<0.05). There was no significant difference between irisin levels in the groups classified in terms of Gleason scores (p>0.05). When the cutoff value was taken as 8.1, the sensitivity and specificity of irisin for PCa were as 80.5% and 90%, respectively. Conclusion: The results of this study indicate that the levels of irisin in the PCa group are considerably reduced and irisin may be used as a biomarker as well as free and total PSA.

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Irisin stimulates cell proliferation and invasion by targeting the PI3K/AKT pathway in human hepatocellular carcinoma

Cited by 73 publications

References 30 publications

MicroRNA‐493‐5p‐mediated repression of the MYCN oncogene inhibits hepatic cancer cell growth and invasion

MicroRNA‐493‐5p‐mediated repression of the MYCN oncogene inhibits hepatic cancer cell growth and invasion

New insights into the cellular activities of Fndc5/Irisin and its signaling pathways

Can the Irisin be a Biomarker for Prostate Cancer? A Case Control Study

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