Degradation of miR-21 induces apoptosis and inhibits cell proliferation in human hepatocellular carcinoma

Najafi, Z; Sharifi, Mohammadreza; Javadi, Gholamreza

doi:10.1038/cgt.2015.51

Cited by 45 publications

(22 citation statements)

References 42 publications

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“…In HCC, miR-122 expression is lower in serum or circulating exosomes of positive patients compared with healthy individuals, but miR-21, on the other hand, is higher in HCC patients [37]. Although miR-122 knockdown inhibits apoptosis and increases HCC cell viability in vitro [34], miR-21 knockdown enhances apoptosis and decreases cell viability [38]. A study using human CCA specimens has revealed elevated miR-21 expression in the CCA tissue compared with noncancerous biliary epithelium.…”

Section: Strong Candidate Biomarkers For Liver Diseasesmentioning

confidence: 99%

Exosomes in liver pathology

Sato

Meng²,

Glaser

et al. 2016

Journal of Hepatology

165

145

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Exosomes are small (~100 nm) membrane-bound extracellular vesicles released by various types of cells into biological fluids. They contain proteins, mRNAs and miRNAs as cargo. Different cell types can take up exosomes by endocytosis and the cargo contained within them can be transferred horizontally to these recipient cells. Exosomal proteins and miRNAs can be functional and regulate physiological cell events modifying the microenvironment in target cells, a key event of liver pathology. Exosome-mediated cell-cell communication can alter tumor growth, cell migration, anti-viral infection and hepatocyte regeneration, indicating that exosomes have great potential development as diagnostic or therapeutic tools. Analyses of circulating total or exosomal miRNAs have identified a large number of candidate miRNAs that are regulated in liver diseases, and the diagnostic testing using single or multiple miRNAs shows good sensitivity and specificity. Some candidate miRNAs have been identified to play an important role in various liver disorders. This review summarizes recent findings on the role of extracellular vesicles in liver diseases and their diagnostic and therapeutic potential, mainly focusing on exosomes but also includes microvesicles in liver pathology.

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Section: Strong Candidate Biomarkers For Liver Diseasesmentioning

confidence: 99%

Exosomes in liver pathology

Sato

Meng²,

Glaser

et al. 2016

Journal of Hepatology

165

145

View full text Add to dashboard Cite

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“…Numerous studies have shed light on tumor-targeting therapies using miRNAs as a novel diagnostic and therapeutic tools (7,8,12,25,28). In the present study, the downregulation of Klf4 and miR-31 was consistently observed in HCC tissues and they may thus serve as potential diagnostic markers and therapeutic targets for HCC.…”

Section: Discussionmentioning

confidence: 99%

Klf4 inhibits tumor growth and metastasis by targeting microRNA-31 in human hepatocellular carcinoma

Tian

Yao

Liu

et al. 2016

International Journal of Molecular Medicine

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MicroRNAs (miRNAs or miRs) are short, endogenous non-coding RNA molecules, demonstrating abnormal expression in cancer initiation and progression. In this study, we profiled 18 differentially regulated miRNAs, including miRNA-31, using miRNA array. Kruppel (or Krüppel)-like factor 4 (Klf4) is a transcription factor and putative tumor suppressor. Both were found to be significantly downregulated in liver cancer tissues and cells. However, little is known about the correlation between Klf4 and miRNA-31 in hepatocellular carcinoma (HCC). The mRNA expression of Klf4 was decreased and inversely associated with the clinical stage, T classification and hepatitis B in patients with HCC, while the expression of miR-31 was lower (r=0.326, P=0.018). Using cell counting kit 8 (CCK8) and Transwell migration assays, we found that Klf4 and miR-31 inhibited the proliferation and metastasis of liver cancer cells. Moreover, we demonstrated that Klf4 directly binds to the promoter of miR-31 and activates its transcription. In vitro experiments confirmed that Klf4 regulated miR-31 and thereby inhibited HCC cell growth and metastasis. Taken together, our findings indicate that Klf4 directly regulates miR-31 in HCC. Thus, miR-31 may serve as a potential diagnostic marker and therapeutic target in HCC.

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“…The cancer cells can depend on oncomiR expression and its downregulation can have potent effect on their survival. Therefore, at the moment miR-21 presents a good candidate and further supports the idea of using miR-21 inhibitors in order to treat human cancers (Sicard et al 2013;Najafi et al 2015).…”

Section: Discussionmentioning

confidence: 81%

Differential response of normal and transformed mammary epithelial cells to combined treatment of anti-miR-21 and radiation

Radulović

Heider

Richter

et al. 2017

International Journal of Radiation Biology

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Purpose: MicroRNA miR-21 has emerged as a therapeutic target in the treatment of breast cancer. This study was designed to compare the responses of breast cancer cells and non-transformed breast epithelial cells to a combined regimen of miR-21 inhibition and radiation. Materials and methods: The MDA-MB-361 (breast cancer) and MCF-10A (non-transformed mammary epithelial) cell lines were used for the comparison in this in vitro study. The stable knockdown of miR-21 was performed by using lentiviral approach. The response of the cells was monitored 4, 24 and 48 h after the irradiation with 0.25 and 2.5 Gy, using sham-irradiated cells as controls. The response of the cells was established by performing various functional assays -cell viability and cell attachment, clonogenic survival, cell cycle analysis and 3D microtissue formation. Results: The knockdown of miR-21 induced significant increase in apoptosis and growth delay in MDA-MB-361 cancer cells compared to non-transformed MCF-10A cells. After combined radiation and anti-miR-21 treatment, MDA-MB-361 cells show reduced cell growth and viability what is presented in their inability to form colonies. MCF-10A cells were not as sensitive to the combined treatment and that has also been confirmed with colony forming assay. Conclusions: Cellular response to a combined treatment of anti-miR-21 and radiation is different between cancer and non-cancer cells which highly support the idea of linking miR-21 inhibitor and radiation treatment in the future therapeutic approaches for breast cancer. ARTICLE HISTORY

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Degradation of miR-21 induces apoptosis and inhibits cell proliferation in human hepatocellular carcinoma

Cited by 45 publications

References 42 publications

Exosomes in liver pathology

Exosomes in liver pathology

Klf4 inhibits tumor growth and metastasis by targeting microRNA-31 in human hepatocellular carcinoma

Differential response of normal and transformed mammary epithelial cells to combined treatment of anti-miR-21 and radiation

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