miR-27a as an Oncogenic microRNA of Hepatitis B Virus-related Hepatocellular Carcinoma

Wu, Ximei; Li, Yan; Liu, Dong; Zhao, Lunde; Bai, Bin; Xue, Minghui

doi:10.7314/apjcp.2013.14.2.885

Cited by 42 publications

(24 citation statements)

References 31 publications

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“…MicroRNAs (miRNAs) are small non-protein coding genes of about 19-23 nucleotides which functions in many biological functions including cell fate specification, cellular proliferation, differentiation, and apoptosis through alteration of the target expression by both downregulation and upregulation [1][2][3]. The correlation within miRNA dictions and tumor prognosis has been documented [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Downregulation of miR-148b as biomarker for early detection of hepatocellular carcinoma and may serve as a prognostic marker

et al. 2015

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MicroRNAs (miRNAs) have a large number of various target genes in different cancer types, which may result in many biological functions. Thus, identifying the molecular mechanisms of miRNAs may effect on the complexity of cancer progression via regulation of gene. In the current study, we utilized real-time PCR to quantify the diction of miR-148b in trail hepatocellular carcinoma (HCC) specimen and normal tissues. Furthermore, we evaluated the relationship of miR-148b and clinicopathological features with survival of HCC patients. Therefore, we evaluated the level of miR-148b expression in 101 HCC patients and also in 40 normal control cases. The result suggested lower expression in tumor tissues than normal control tissues (0.96 ± 0.14; 1.84 ± 0.20, P < 0.05). Our findings suggest that the declined expression of miR-148b can considerably be linked to tumor node metastasis (TNM) stage (stages III and IV; P = 0.021) and vein invasion (P = 0.029). Nevertheless, miR-148b expression was not related to sex (P = 0.674), age (P = 0. 523), size of tumor (P = 0.507), liver cirrhosis, and histologic grade (P = 0.734). Survival analysis showed that low expression was remarkably related to overall survival (P = 0.012). Furthermore, multivariate survival test suggested that decline of miR-148b diction was linked to poor survival in HCC patients. Our results suggested that miR-148b is decreased in HCC. Therefore, we concluded that miR-148b may play its role in the prognosis of HCC.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Downregulation of miR-148b as biomarker for early detection of hepatocellular carcinoma and may serve as a prognostic marker

et al. 2015

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“…These miRNAs are short-strand molecules and have about 19-23 nucleotides in length which play a key role in many biological functions such as cell fate specification, cellular proliferation, differentiation, and apoptosis [1][2][3][4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Profiles of tissue microRNAs; miR-148b and miR-25 serve as potential prognostic biomarkers for hepatocellular carcinoma

et al. 2015

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The early diagnosis of hepatocellular carcinoma is challenging because it requires specific biomarkers. It has been determined that deregulation or dysfunction of microRNAs (miRNAs) could contribute to development of cancer. The aim of this research was to evaluate the main role of tissue miRNAs as prognostic biomarkers for early diagnosis of hepatocellular carcinoma. We used quantitative real-time PCR to evaluate the level of miR-148b and miR-25 expressions in hepatocellular carcinoma (HCC) patients and normal tissues and their relationship with clinicopathological features and survival in HCC patients. Quantitative real-time PCR was observed that median relative expression of miR-148b decreased in tumors tissue compared with normal tissues (P<0.05), while overexpression of miR-25 was observed in HCC tissues in comparison with normal tissues (P<0.003). The results suggested that the low level of miR-148b expression was remarkably related to tumor-node-metastasis (TNM) stage (stages III and IV; P=0.024) and vein invasion (P=0.032). Nevertheless, there was no significantly relationship of miR-148b expression with other clinical factors including sex (P = 0.612), age (P=0.536), size of tumor (P=0.513), and hepatic cirrhosis (P = 0.417). Moreover, increased level of miR-25 expression was remarkably associated with TNM stage (P=0.013). Kaplan-Meier survival and log-rank test confirm that shorter overall survival was strongly linked to decreased expression of miR-148b (P=0.004), while high expression of miR-25 was associated with shorter time survival than that patient with low level of miR-25 expression (P = 0.027). The result of multivariate Cox proportional hazards model suggested that low miR-148b expression, high miR-25 expression TNM stage, and vein invasion were independently related to poor survival of HCC patients in terms of miR-148b and miR-25 (Tables 3 and 4). Our results indicated that downregulation of miR-148b could play a role as an independent prognostic factor in patients with HCC. Furthermore, miR-25 can be as a prognostic marker and high expression of miR-25 has predictive value for poor prognosis in HCC patients.

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“…* p < 0.05; ** p < 0.01 vs NC group; # p < 0.05; ## p < 0.01. by comparing alteration in the expression of miRNA profiles between HepG2 and HepG2/5-FU cells (Table 1), it was observed that the majority of the highly expressed miRNAs in 5-FU-resistant cells exhibited the properties of oncogenes, such as miR-21, miR-27a, and miR-155 [14][15][16]. Reduced expression of miRNAs, such as miR-340, miR-145, and miR-451 was previously described as tumor suppression [17].…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

MiR-141 Activates Nrf2-Dependent Antioxidant Pathway via Down-Regulating the Expression of Keap1 Conferring the Resistance of Hepatocellular Carcinoma Cells to 5-Fluorouracil

Shi

Wu²,

Chen³

et al. 2015

Cell Physiol Biochem

112

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Background: Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide. A major cause for the failure of cancer therapy is the development of chemoresistance. Although progress has been made in the study of the mechanisms underlying cancer cells resistance, little is known about the role of microRNAs (miRNAs) in cancer therapy resistance. Methods and Results: Fifteen miRNAs, including 6 up-regulated miRNAs (> 2.0-fold) and 9 down-regulated miRNAs (< 0.5-fold) were differentially expressed in 5-fluorouracil-resistant and their parental cell-lines (HepG2, HepG2/5-FU) by miRNA microarrays. Microarray results were confirmed by validating quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Up-regulation of miR-141 expression resulted in a significant inhibition of 5-FU-mediated cytotoxicity and apoptosis in various hepatocellular carcinoma cells-lines. Mechanically, miR-141 promoted Kelch-like ECH-associated protein 1 (Keap1) mRNA degradation by directly targeting the Keap1 3'untranslated region (3'UTR). Treatment with miR-141 mimics in parental HepG2 cells, restored miR-141 expression and reduced Keap1 levels, thereby resulting in erythroid transcription factor NFE2-L2 (Nrf2) nuclear translocation, activation of Nrf2-dependent HO-1 gene transcription, and subsequent enhancement in 5-FU resistance. Conversely, restoring the expression of Keap1 partly recovered 5-FU sensitivity by counteracting miR-141-mediated 5-FU resistance. Conclusion: Our study showed that miR-141 plays a key role in 5-FU resistance by down-regulating Keap1 expression, thereby reactivating the Nrf2-dependent antioxidant pathway, which may serve as a potential target for overcoming 5-FU resistance in hepatocellular carcinoma cells.

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miR-27a as an Oncogenic microRNA of Hepatitis B Virus-related Hepatocellular Carcinoma

Cited by 42 publications

References 31 publications

RETRACTED ARTICLE: Downregulation of miR-148b as biomarker for early detection of hepatocellular carcinoma and may serve as a prognostic marker

RETRACTED ARTICLE: Downregulation of miR-148b as biomarker for early detection of hepatocellular carcinoma and may serve as a prognostic marker

RETRACTED ARTICLE: Profiles of tissue microRNAs; miR-148b and miR-25 serve as potential prognostic biomarkers for hepatocellular carcinoma

MiR-141 Activates Nrf2-Dependent Antioxidant Pathway via Down-Regulating the Expression of Keap1 Conferring the Resistance of Hepatocellular Carcinoma Cells to 5-Fluorouracil

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