MicroRNA-424 Is Down-Regulated in Hepatocellular Carcinoma and Suppresses Cell Migration and Invasion through c-Myb

Yu, Long-Chuan; Ding, Guo-feng; He, Chao; Sun, Lei; Jiang, Yanfang; Zhū, Lìyǐng

doi:10.1371/journal.pone.0091661

Cited by 79 publications

(69 citation statements)

References 41 publications

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“…For example, miR-191, an oncogenic miRNA, was shown to be highly expressed in HCC and involved in cell proliferation, apoptosis and epithelial mesenchymal transition in HCC, and its hypomethylation has been proved to be associated with poor prognosis [32], interestingly, here we found miR-191 could be down-regulated by baicalein; miR-222-5p and miR-675 were reported to be up-regulated in HCC tumor tissues and positively associated with recurrence after resection [33], whereas our result showed that they were both down-regulated under baicalein treatment; miR-424-3p has been demonstrated to be down-regulated in HCC and suppresses tumor growth, cell migration and invasion through its downstream target Akt3, E2F3 and c-Myb [34, 35], nevertheless, we found miR-424-3p could be up-regulated by baicalein. In addition, previous studies have demonstrated that baicalein is able to inhibit the proliferation, invasion and metastasis of HCC through inducing cell cycle arrest and apoptosis via several cancer-related signaling including MEK/ERK, JNK, mTOR, NF-κB etc [5, 6].…”

Section: Discussionmentioning

confidence: 69%

Baicalein, a Natural Anti-Cancer Compound, Alters MicroRNA Expression Profiles in Bel-7402 Human Hepatocellular Carcinoma Cells

Bie

Sun

et al. 2017

Cell Physiol Biochem

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Background/Aims: Baicalein has been shown to possess significant anti-hepatoma activity by inhibiting cell proliferation. Whether the anti-proliferative effect of baicalein is related to its modulation of miRNA expression in hepatocellular carcinoma (HCC) is still unknown. Methods: The anti-proliferative effects of baicalein on HCC cell line Bel-7402 was assessed by detecting the proliferation activity, cell cycle distribution, expression changes of p21/CDKN1A, P27/CDKN1B, total Akt and phosphoryted AKT. Microarray analysis was conducted to determine the miRNA expression profiles in baicalein-treated or untreated Bel-7402 cells and then validated by qRT-PCR in two HCC cell lines (Bel-7402 and Hep3B). The gain-of-function of miR-3127-5p was performed by detecting anti-proliferative effects after transfecting miRNA mimics in cells. Finally, the expression level of miR-3127-5p in different HCC cell lines was determined by qRT-PCR. Results: Baicalein was able to inhibit the proliferation of Bel-7402 cells by inducing cell cycle arrest at the S and G2/M phase via up-regulating the expression of p21/CDKN1A and P27/CDKN1B and suppressing the PI3K/Akt pathway. Baicalein could alter the miRNA expression profiles in Bel-7402 cells. Putative target genes for differentially expressed miRNAs could be enriched in terms of cell proliferation regulation, cell cycle arrest and were mainly involved in MAPK, PI3K-Akt, Wnt, Hippo and mTOR signaling pathways. MiR- 3127-5p, one of up-regulated miRNAs, exhibits low expression level in several HCC cell lines and its overexpression could inhibit cell growth of Bel-7402 and Hep3B cell lines by inducing S phase arrest by up-regulating the expression of p21and P27 and repressing the PI3K/Akt pathway. Conclusions: Modulation of miRNA expression may be an important mechanism underlying the anti-hepatoma effects of baicalein.

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Section: Discussionmentioning

confidence: 69%

Baicalein, a Natural Anti-Cancer Compound, Alters MicroRNA Expression Profiles in Bel-7402 Human Hepatocellular Carcinoma Cells

Bie

Sun

et al. 2017

Cell Physiol Biochem

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“…MiRNAs play their roles through binding to their target mRNAs and inhibiting their protein expressions [38–40]. In our study, we identified ROCK1 as a direct target of miR-300 in glioblastoma.…”

Section: Discussionmentioning

confidence: 75%

MicroRNA-300 inhibited glioblastoma progression through ROCK1

Zhou

et al. 2016

Oncotarget

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Glioblastoma is a common type of brain aggressive tumors and has a poor prognosis. MicroRNAs (miRNAs) are a class of small, endogenous and non-coding RNAs that play crucial roles in cell proliferation, survival and invasion. Deregulated expression of miR-300 has been studied in a lot of cancers. However, the role of miR-300 in glioblastoma is still unknown. In this study, we demonstrated that miR-300 expression was downregulated in glioblastoma tissues compared with the normal tissues. Lower expression level of miR-300 was observed in thirty cases (75 %, 30/40) of glioblastoma samples compared with the normal samples. Moreover, the overall survival of glioblastoma patients with lower miR-300 expression level was shorter than those with higher miR-300 expression level. In addition, miR-300 expression was also downregulated in glioblastoma cell lines. Overexpression of miR-300 inhibited cell proliferation, cell cycle and invasion in glioblastoma cell line U87 and U251. Moreover, we identified ROCK1 as a direct target of miR-300 in U87 and U251 cells. Overexpression of ROCK1 partially rescued the miR-300-mediated cell growth. ROCK1 expression levels in glioblastoma tissues were higher than that in normal tissues. ROCK1 expression levels were higher in thirty-one cases of glioblastoma samples than their normal samples. Furthermore, the expression level ROCK1 was inversely correlated with the expression level of miR-300. Importantly, overexpression of miR-300 suppressed glioblastoma progression in an established xenograft model. In conclusion, we revealed that miR-300 might act as a tumor suppressor gene through inhibiting ROCK1 in glioblastoma.

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“…For instance, miR-125a, which is always significantly downregulated in HCC, inhibits the metastasis of tumor cells by targeting MMP11 and vascular endothelial growth factor A (VEGF-A) [89]. Similarly, miR-424, which is also down-regulated in HCC, suppresses tumor cell migration and invasion through its downstream target cMyb [90]. Other key signaling molecules that promote metastasis of HCC are targeted by miRNAs, including a disintegrin and metalloprotease 17 (ADAM17), metastasis suppressor 1 (MTSS1), type I collagen alpha2 (COL1A2), and other factors [91][92][93].…”

Section: Deregulated Mirnas In Invasion and Metastasismentioning

confidence: 99%

miRNAs affect the development of hepatocellular carcinoma via dysregulation of their biogenesis and expression

Chu

Duan

et al. 2014

Cell Communication and Signaling

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The pathogenesis of hepatocellular carcinoma (HCC) is not fully understood, which has affected the early diagnosis and treatment of HCC and the survival time of patients. MicroRNAs (miRNAs) are a class of evolutionarily conserved small, non-coding RNAs, which regulate the expression of various genes post-transcriptionally. Emerging evidence indicates that the key enzymes involved in the miRNA biosynthesis pathway and some tumor-specific miRNAs are widely deregulated or upregulated in HCC and closely associated with the occurrence and development of various cancers, including HCC. Early studies have shown that miRNAs have critical roles in HCC progression by targeting many critical protein-coding genes, thereby contributing to the promotion of cell proliferation; the avoidance of apoptosis, inducing via angiogenesis; and the activation of invasion and metastasis pathways. Experimental data indicate that discovery of increasing numbers of aberrantly expressed miRNAs has opened up a new field for investigating the molecular mechanism of HCC progression. In this review, we describe the current knowledge about the roles and validated targets of miRNAs in the above pathways that are known to be hallmarks of HCC, and we also describe the influence of genetic variations in miRNA biosynthesis and genes.

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MicroRNA-424 Is Down-Regulated in Hepatocellular Carcinoma and Suppresses Cell Migration and Invasion through c-Myb

Cited by 79 publications

References 41 publications

Baicalein, a Natural Anti-Cancer Compound, Alters MicroRNA Expression Profiles in Bel-7402 Human Hepatocellular Carcinoma Cells

Baicalein, a Natural Anti-Cancer Compound, Alters MicroRNA Expression Profiles in Bel-7402 Human Hepatocellular Carcinoma Cells

MicroRNA-300 inhibited glioblastoma progression through ROCK1

miRNAs affect the development of hepatocellular carcinoma via dysregulation of their biogenesis and expression

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