MiR-124 suppresses cell proliferation in hepatocellular carcinoma by targeting PIK3CA

Lang, Qing-bo; Ling, Changquan

doi:10.1016/j.bbrc.2012.08.075

Cited by 127 publications

(85 citation statements)

References 24 publications

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“…Although several miRNAs with deregulated expression have been observed in HCC [10,22,23], the molecular mechanisms by which miRNAs modulate the processes of carcinogenesis and cancer progression remain largely unknown. Understanding the roles of deregulated miRNAs in cancer development, specifically those detected by MPSS of the miRNomes, may help to reveal not only the abnormally expressed miRNAs, but also the abundance of individual miRNAs in the entire miRNome, and even reveal the underlying mechanisms of HCC carcinogenesis and progression.…”

Section: Discussionmentioning

confidence: 99%

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MicroRNA‐486‐5p, which is downregulated in hepatocellular carcinoma, suppresses tumor growth by targeting PIK3R1

et al. 2014

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Deregulated microRNAs and their roles in carcinogenesis and cancer progression have attracted much attention. In previous studies conducted in our laboratory, the Illumina Solexa massively parallel signature sequencing of miRNomes in nontumor and hepatocellular carcinoma (HCC) tissues revealed that miR-486-5p was significantly downregulated in HCC, but its role in HCC development remains unknown. In this study, miR-486-5p levels in HCC tissues and matched control tissues, and in seven HCC cell lines (QGY-7701, QGY-7703, QGY-7404, SMMC-7721, Huh7, HepG2, and PCL/PRF/5) and human normal liver cells (HL-7702), were tested by real-time quantitative RT-PCR. We found that the level of miR-486-5p was significantly decreased in HCC tissue and in all seven HCC cell lines. Overexpression of miR-486-5p markedly suppressed HCC cell proliferation, migration and invasion in vitro, and inhibited HCC growth in vivo. Mechanistically, miR-486-5p was confirmed to directly target PIK3R1 expression, thereby suppressing phosphatidylinositol 3-kinase-AKT pathway activation, by dual luciferase reporter assay and real-time quantitative RT-PCR and western blot analysis. In addition, PIK3R1 knockdown mimicked the effects of miR-486-5p overexpression by inhibiting HCC growth, migration, and invasion. Furthermore, correlation analysis, Kaplan-Meier estimates and Cox proportional hazard models showed an inverse correlation between miR-486-5p and PIK3R1, as well as a shorter time to recurrence after HCC resection, in patients with lower miR-486-5p expression. Hence, we conclude that miR-486-5p, which is frequently downregulated in HCC, inhibits HCC progression by targeting PIK3R1 and phosphatidylinositol 3-kinase-AKT activation. DatabaseThe Solexa sequencing data are available in GEO database (www.ncbi.nlm.nih.gov/geo/) under accession number GSE21279.Abbreviations DFS, disease-free survival; FACS, fluorescence-activated cell sorting; GSK3b, glycogen synthase kinase-3b; HCC, hepatocellular carcinoma; miRNA, microRNA; MPSS, massively parallel signature sequencing; PI3K, phosphatidylinositol 3-kinase; qRT-PCR, quantitative RT-PCR; SD, standard deviation.

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Section: Discussionmentioning

confidence: 99%

“…MicroRNAs (miRNAs) are small, noncoding RNAs of [19][20][21][22][23] nucleotides that negatively regulate gene expression by binding to the untranslated regions of target mRNAs [8]. Bioinformatics analysis predicts that miRNAs can affect up to 30% of all human genes [9].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‐486‐5p, which is downregulated in hepatocellular carcinoma, suppresses tumor growth by targeting PIK3R1

et al. 2014

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“…These catalytic subunits are regulated by miRNAs. For example, the overexpression of miR-124 leads to the downregulation of PIK3CA [95]; furthermore, miR-7 targets PIK3CD, mTOR, and p70S6K [96], both of which result in suppression of the PI3K/Akt/ mTOR-signaling pathway. These facts indicate that miRNAs could act as tumor regulators by suppressing PI3K to inhibit the metastasis of HCC.…”

Section: Deregulated Mirnas In Pi3k/akt/mtor/autophagy Pathwaymentioning

confidence: 99%

“…The hallmark of autophagy is the transition of LC3-I to its lipidated form (LC3-II), which requires the help of autophagy-related-gene 7 (Atg 7) [95]. To date, two miRNAs were demonstrated to be related to the autophagy process of HCC.…”

Section: Deregulated Mirnas In Pi3k/akt/mtor/autophagy Pathwaymentioning

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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“…For clinical treatment, supplementing the down-regulated expression of microRNA in the patients of HCC would be a good strategy. MicroRNA replacement therapy of primary HCC has been applied in a mouse model and the demonstrated systems complementing microRNA-6a, -122 and -124 can reduce tumorigenesis and metastasis of HCC [33,34]. By contrast, the inhibition of onco-miR-221 can prolong survival and shrink the volume of a tumor [35,36].…”

Section: Micrornas As a Biomarker In The Diagnosis And Treatment Of Hccmentioning

confidence: 99%

MicroRNAs in the Occurrence and Development of Primary Hepatocellular Carcinoma

Zheng

et al. 2016

Adv Clin Exp Med

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MiR-124 suppresses cell proliferation in hepatocellular carcinoma by targeting PIK3CA

Cited by 127 publications

References 24 publications

MicroRNA‐486‐5p, which is downregulated in hepatocellular carcinoma, suppresses tumor growth by targeting PIK3R1

MicroRNA‐486‐5p, which is downregulated in hepatocellular carcinoma, suppresses tumor growth by targeting PIK3R1

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

MicroRNAs in the Occurrence and Development of Primary Hepatocellular Carcinoma

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