MiR-424-5p reversed epithelial-mesenchymal transition of anchorage-independent HCC cells by directly targeting ICAT and suppressed HCC progression

Zhang, Ying; Li, Tao; Guo, Pengbo; Kang, Jia; Wei, Qing; Xing, Jia; Zhao, Wei; Huai, Wanwan; Qiu, Yumin; Han, Lihui

doi:10.1038/srep06248

Cited by 97 publications

(89 citation statements)

References 39 publications

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“…(24) Zhang et al reported that the anoikis-resistant process of HCC cells was also accompanied by the EMT process, whereas the miRNA miR-424-5p could prevent HCC progression by reversing these two processes that are critically involved in metastasis. (25) In this study, MHCC97H-H cells formed more colonies in soft agar; coupled with their promoted metastatic ability in vivo, these data suggested that EMT-like cells are more resistant to anoikis.…”

Section: Discussionsupporting

confidence: 57%

Effect of a Hypoxic Microenvironment after Radiofrequency Ablation on Residual Hepatocellular Cell Migration and Invasion

Tong

Luo

2017

Ultrasound in Medicine & Biology

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Clinical observations have shown that the boundary of tumor ablation is often less than safe border and that the use of radiofrequency ablation (RFA) in the treatment of hepatocellular carcinoma (HCC) may probably accelerate its recurrence and metastasis. RFA can cause the formation of a transition zone between normal liver tissues and necrotic coagulation, where blood stagnation and thrombosis expose residual cancer cells to a hypoxic microenvironment. As the blocked vessels are slowly reperfused, the oxygen supply is gradually restored. Here, HCC cells underwent heat treatment and were cultured under hypoxic conditions to mimic the aforementioned situation, and morphological changes were observed in the surviving cells. Compared with their parental cells, hypoxic HCC cells showed changes that include enhanced invasive, metastatic, and chemoresistant abilities as well as mesenchymal characteristics. There was also a higher percentage of stem-like cells. However, either improving the hypoxic microenvironment or silencing hypoxia inducible factor (HIF)-1a signaling significantly reduced the invasive, metastatic, and chemoresistant potential and reversed the epithelialmesenchymal transition to varying degrees. Together, these results indicated that a sustained hypoxic microenvironment after RFA may exert a negative impact on the prognosis of HCC patients, and minimizing exposure to a hypoxic microenvironment and targeting HIF-1a signaling might be effective strategies for patients who experience insufficient RFA therapy.H epatocellular carcinoma (HCC) ranks as the third most frequent cause of cancer-related death.(1) Although surgical operation and transplantation have been recognized as the primary curative therapies for patients with HCC, the advanced neoplastic stage, severe liver dysfunction and shortage of available liver grafts restrict their application.(2) Radiofrequency ablation (RFA) therapy has emerged as an alternative due to its minimal invasiveness, safety, and shorter hospital stays. The survival of patients with HCC <3 cm treated by RFA competes with that of surgical candidates.(3) However, suboptimal RFA treatment of HCC has been reported as a risk factor of early diffuse recurrence, (4) and large tumor size is an independent risk factor of local recurrence because of its poorly defined margins.(5) The necrotic lesion generated by RFA is surrounded by a rim of chronically hypoxic liver tissue, where aggressive outgrowth of residual hepatic micro-metastases has been observed.(6) A hypoxic microenvironment contributes to the development of a malignant phenotype, which includes local invasion, metastatic progression, and chemoresistance. Hypoxia inducible factor (HIF)-1a is a key mediator of cellular adaption to hypoxia (8) and can facilitate the progression of various cancer cells by promoting cell migration, tumor angiogenesis, and metastasis.(9) The epithelial-mesenchymal transition (EMT) has long been recognized as an important step in the progression of primary tumors to distant metastasis.(10) ...

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Section: Discussionsupporting

confidence: 57%

Effect of a Hypoxic Microenvironment after Radiofrequency Ablation on Residual Hepatocellular Cell Migration and Invasion

Tong

Luo

2017

Ultrasound in Medicine & Biology

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“…It indicated that sorafenib-resistant HCC cells was associated with an upregulated miR-10a-5p level, which implies that miR-10a-5p has its own spatio- temporal expression in HCC (Tang et al 2016). The mechanism explorations of miR-199a-3p, miR-424-5p and miR-195-5p have demonstrated that they all act as tumor suppressors in HCC (Fornari et al 2010;Zhang et al 2014;Xu et al 2015). In summary, our study applied the Agilent microarray to determine expression profiles of the miRNAs in HCC specimens.…”

Section: Discussionmentioning

confidence: 99%

Microarray Expression Profiling of microRNAs Reveals Potential Biomarkers for Hepatocellular Carcinoma

Zhu

Huang

et al. 2018

Tohoku J. Exp. Med.

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Hepatocellular carcinoma (HCC) remains a major health problem for delayed diagnosis, inefficient surveillance and poor prognosis. Recent studies have indicated that non-coding RNAs contribute to the development of new strategies for diagnosis and treatment of HCC. In the present study, we employed 18 pairs of HCC and matched non-tumor tissues for the identification of differentially expressed microRNAs (miRNAs) in HCC, among which 7 paired specimens were selected randomly for microarray detection. Totally, twenty-three miRNAs were screened out to have statistically significant differences with the threshold of P < 0.01 and fold-change ≥ 2.0 or ≤ 0.5 using miRNA microarray. In the validation stage, two miRNAs exhibited higher expression levels in the HCC tissues compared with those in the matched non-tumor tissues, whereas the expression levels of ten miRNAs were lower in the HCC tissues than those in the matched non-tumor tissues. In further analysis, eight miRNAs, including miR-4270, miR-125b-5p, miR-199a-3p, miR-10a-5p, miR-424-5p, miR-195-5p, miR-106b-5p and miR-3651, were retained, when another constraint about the signal intensity of microarray probes was established. Among these miRNAs, our study was the first to show the higher expression level of miR-3651 and the lower expression level of miR-4270 in HCC. The areas under the receiver-operating-characteristic curve values of miR-3651 and miR-4270 were 0.730 and 0.967, respectively, indicating their potential diagnostic values. Our results may help provide the context for expanded interpretations of miRNA studies involved in the progression of liver disease, potentially serving as a diagnostic tool of HCC.

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“…The proliferation status of cells were detected at different time points, including 0, 12 h, 24 h, 36 h, 48 h, and 72 h. Cell invasion and colony formation assay were performed as described before [26, 27]. …”

Section: Methodsmentioning

confidence: 99%

Loss of AIM2 expression promotes hepatocarcinoma progression through activation of mTOR-S6K1 pathway

et al. 2016

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Absent in melanoma (AIM2) is a member of the interferon-inducible HIN-200 protein family and is recently recognized to play an important dual role in both innate immunity and tumor pathology. However, the role of AIM2 in the development of hepatocellular carcinoma (HCC) remains to be clarified. Here we showed that AIM2 expression was significantly decreased in liver cancer tissues, and loss of its expression was significantly correlated with more advanced tumor progression. Exogenous overexpression of AIM2 in HCC cells suppressed mammalian target of rapamycin (mTOR)-S6K1 pathway and further inhibited proliferation, colony formation and invasion of HCC cells. On the contrary, block of AIM2 in HCC cells induced (mTOR)-S6K1 pathway activation and thus promoted HCC progression. Treatment with mTOR pathway inhibitor rapamycin further verified its contribution to HCC progression in AIM2 absent HCC cells. Thus, these data suggested that AIM2 played a critical role as a tumor suppressor and might serve as a potential therapeutic target for future development of AIM2-based gene therapy for human liver cancer. This study also paves a new avenue to treat AIM2-deficient cancer by suppression of mTOR.

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MiR-424-5p reversed epithelial-mesenchymal transition of anchorage-independent HCC cells by directly targeting ICAT and suppressed HCC progression

Cited by 97 publications

References 39 publications

Effect of a Hypoxic Microenvironment after Radiofrequency Ablation on Residual Hepatocellular Cell Migration and Invasion

Effect of a Hypoxic Microenvironment after Radiofrequency Ablation on Residual Hepatocellular Cell Migration and Invasion

Microarray Expression Profiling of microRNAs Reveals Potential Biomarkers for Hepatocellular Carcinoma

Loss of AIM2 expression promotes hepatocarcinoma progression through activation of mTOR-S6K1 pathway

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