The function of miRNAs in hepatocarcinogenesis induced by hepatitis B virus X protein

Wang, Ziyao; Wu, Zhongjun; Huang, Ping

doi:10.3892/or.2017.5716

Cited by 16 publications

(9 citation statements)

References 130 publications

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“…For example, miR-34a,9 miR-506,10 and miR-64511 are downregulated in HCC, whereas miR-197,12 miR-552,13 and miR-65014 are expressed at high levels in HCC. The dysregulated miRNAs exert their functions as oncogenes or tumor suppressors and play crucial roles in the initiation and progression of HCC 15–17. Therefore, therapies that target miRNAs may be attractive strategies for HCC treatment.…”

Section: Introductionmentioning

confidence: 99%

microRNA-944 inhibits the malignancy of hepatocellular carcinoma by directly targeting IGF-1R and deactivating the PI3K/Akt signaling pathway

Lv¹,

Wang²,

Ma³

2019

CMAR

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Purpose: Recent studies have identified microRNA-944 (miR-944) as a cancer-related miRNA, but its expression and precise functions in hepatocellular carcinoma (HCC) remain unknown. Patients and methods: miR-944 expression in HCC tissues and cell lines were detected by RT-qPCR. A series of functional assays were utilized to examine the influence of miR-944 on the malignant phenotypes of HCC cells in vitro and in vivo. More importantly, the associated mechanisms underlying the activity of miR-944 in HCC cells were investigated using bioinformatics, luciferase reporter assays, RT-qPCR, and western blot analysis. Results: In this study, we report for the first time, a significant downregulation of miR-944 in HCC tissues and cell lines and the correlation between its downregulation and malignant clinical parameters, including Edmondson-Steiner grade, TNM stage, and venous infiltration. Low miR-944 expression predicted poorer overall survival rate and disease-free survival rate in patients with HCC. Functionally, exogenous miR-944 expression attenuated cell proliferation, clone formation, metastasis, and epithelial-mesenchymal transition and increased apoptosis in HCC, whereas miR-944 knockdown produced the opposite results. In addition, ectopic miR-944 expression hindered HCC tumor growth in vivo. Mechanistically, insulin-like growth factor 1 receptor (IGF-1R) was demonstrated to be the direct target gene of miR-944 in HCC cells. Furthermore, the expression level of miR-944 was inversely correlated with IGF-1R expression in HCC tissues. Rescue experiments showed that IGF-1R was at least partially responsible for the effects of miR-944 on the malignant phenotypes of HCC cells. In addition, the PI3K/Akt pathway was notably deactivated, both in vitro and in vivo, upon miR-944 upregulation. Conclusion: This study provides the first evidence that miR-944 directly targets IGF-1R and inhibits the aggressiveness of HCC, in vitro and in vivo, by decreasing PI3K/Akt signaling. Hence, targeting miR-944 may open a new avenue for the treatment of patients with HCC.

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Section: Introductionmentioning

confidence: 99%

microRNA-944 inhibits the malignancy of hepatocellular carcinoma by directly targeting IGF-1R and deactivating the PI3K/Akt signaling pathway

Lv¹,

Wang²,

Ma³

2019

CMAR

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“…[34][35][36] An increasing number of studies have proven that miRNAs are the main drivers of HCC tumorigenesis because they function as oncogenes or tumor suppressor genes. [37][38][39] Moreover, miRNA-based targeted therapies have been tested in several preclinical models, including HCC models. 40 Therefore, identification of oncogenic or tumor-suppressive miRNAs and detailed elucidation of their roles in HCC pathogenesis may help identify effective biomarkers for HCC diagnosis and prognosis as well as therapeutic targets in this cancer.…”

Section: Discussionmentioning

confidence: 99%

microRNA-548b suppresses aggressive phenotypes of hepatocellular carcinoma by directly targeting high-mobility group box 1 mRNA

Yun¹,

Meng²,

Jiang³

et al. 2019

CMAR

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Background and purpose: An increasing number of studies have revealed that microRNAs (miRNAs) are the main drivers of hepatocarcinogenesis including progression to later stages of liver cancer. Recently, miR-548b was identified as a cancer-related miRNA in glioma and tongue squamous cell carcinoma. Nonetheless, the expression pattern and specific roles of miR-548b in hepatocellular carcinoma (HCC) have not yet been clarified. Methods: Expression levels of miR-548b in HCC tissues and cell lines were measured by reverse-transcription quantitative PCR. In vitro and in vivo functional assays were performed to determine the effects of miR-548b on the malignant phenotypes of HCC cells. In addition, the molecular mechanisms by which miR-548b regulates the initiation and progression of HCC were investigated in detail. Results: miR-548b expression was weak in HCC tissues and cell lines. The low miR-548b expression significantly correlated with tumor size, TNM stage, and venous infiltration of HCC. In addition, exogenous miR-548b expression suppressed HCC cell proliferation, colony formation, and metastasis and induced apoptosis in vitro. Silencing of miR-548b exerted an opposite effect on these characteristics of HCC cells. Furthermore, miR-548b overexpression hindered tumor growth in vivo. Mechanistic analysis identified high-mobility group box 1 (HMGB1) as a direct target gene of miR-548b in HCC cells. Moreover, an HMGB1 knockdown reproduced the effects of miR-548b upregulation on HCC cells. Recovered HMGB1 expression reversed the effects of miR-548b on HCC cells. Notably, miR-548b overexpression deactivated the PI3K-AKT pathway in HCC cells in vitro and in vivo. Conclusion: Our findings provide the first evidence that miR-548b restrains HCC progression, at least partially, by downregulating HMGB1 and deactivating the PI3K-AKT pathway. Thus, miR-548b might be a novel target for the development of new therapies for HCC.

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“…Many studies have confirmed that miRNAs are involved in the proliferation, differentiation, migration, and apoptosis of liver cancer cells. 2 It is well known that miR-183 is upregulated in HCC and is considered to be an oncomiR. Functionally, the miR-183 family (miR-183, -96 and -182) promotes the cellular invasion and migration of HCC cells.…”

Section: Introductionmentioning

confidence: 99%

miR-183-5p promotes proliferation and migration in hepatocellular carcinoma by targeting IRS1 and its association with patient survival

Yan

Yuan

et al. 2020

Int J Biol Markers

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Background: MiR-183-5p plays an important role in the pathophysiology of many tumors, while the role of MiR-183-5p in liver cancer is unclear. Methods: In this study, quantitative reverse transcription-polymerase chain reaction and Western blotting were used to detect the expression of miR-183-5p in liver cancer cell lines, liver cancer tissues, and normal tissues adjacent to the cancer, and to explore the mechanism of miR-183-5p regulating liver cancer progression. The in vitro effects of miR-183-5p were evaluated by CCK-8, colony formation test, and wound healing test. Various databases were used to predict the target mRNA of miR-183-5p and verified by luciferase report analysis. In addition, the effects of miR-183-5p and its target gene on the survival of patients with liver cancer were also analyzed. Results: miR-183-5p was highly expressed in hepatocellular carcinoma cells and tissues, and was related to some clinicopathological features. MiR-183-5p can promote the proliferation and migration of liver cancer cells. Using the bioinformatics database, we proved that miR-183-5p is related to the survival of liver cancer patients. Insulin receptor substrate 1 (IRS1) is a target of miR-183-5p, and luciferase analysis confirmed that miR-183-5p combines with the 3′-untranslated region (3′-UTR) of IRS1. Conclusion: The miR-183-5p/IRS1 axis may be a new target for liver cancer research.

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The function of miRNAs in hepatocarcinogenesis induced by hepatitis B virus X protein

Cited by 16 publications

References 130 publications

<p>microRNA-944 inhibits the malignancy of hepatocellular carcinoma by directly targeting IGF-1R and deactivating the PI3K/Akt signaling pathway</p>

<p>microRNA-944 inhibits the malignancy of hepatocellular carcinoma by directly targeting IGF-1R and deactivating the PI3K/Akt signaling pathway</p>

<p>microRNA-548b suppresses aggressive phenotypes of hepatocellular carcinoma by directly targeting high-mobility group box 1 mRNA</p>

miR-183-5p promotes proliferation and migration in hepatocellular carcinoma by targeting IRS1 and its association with patient survival

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