MiR-138 induces cell cycle arrest by targeting cyclin D3 in hepatocellular carcinoma

Wang, Wen; Zhao, Lan‐Juan; Tan, Ye-Xiong; Ren, Hao; Qi, Zhongtian

doi:10.1093/carcin/bgs113

Cited by 192 publications

(160 citation statements)

References 49 publications

(48 reference statements)

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“…These miRs participate in the development and malignant progression of human cancer by negatively regulating the expression of their target genes, which act as oncogenes or tumor suppressors (4). Previously, the deregulation of specific miRs has been identified in HCC, including miR-148a, miR-203, miR-138, miR-122 and miR-124 (6)(7)(8)(9). Therefore, these miRs may become potential therapeutic targets or candidates for HCC treatment (4,10).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-30a-5p suppresses proliferation, invasion and tumor growth of hepatocellular cancer cells via targeting FOXA1

et al. 2017

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Abstract. Deregulation of microRNAs (miRs) has been observed in a variety of types of human cancer. Previously, miR-30a-5p has been demonstrated to exhibit a suppressive role in hepatocellular carcinoma (HCC). However, the underlying mechanism remains largely unclear. The present study aimed to elucidate the regulatory mechanism of miR-30a-5p in proliferation and invasion of HCC cells. Quantitative reverse transcription polymerase and western blotting were used to examine mRNA and protein expression of Forkhead box A1 (FOXA1). MTT and Transwell assays were performed to examine proliferation and invasion. Luciferase reporter assay was used to determine the association between miR-30a-5p and FOXA1. The data indicated that miR-30a-5p was significantly downregulated in HCC tissues compared with normal liver tissues. Furthermore, the level of miR-30a-5p was lower in HCC tissues with higher histological grade and advanced tumor stage compared with tissues with lower histological grade and tumor stage. Additionally, restoration of miR-30a-5p expression decreased the proliferation and invasion of HCC HepG2 and SMMC-7721 cells. FOXA1, a novel oncogene in HCC, was further identified as a target of miR-30a-5p. Furthermore, high expression of miR-30a-5p suppressed mRNA and protein expression of FOXA1, while overexpression of FOXA1 reversed the suppressive effect of miR-30a-5p on proliferation and invasion of HepG2 and SMMC-7721 cells. FOXA1 was markedly upregulated in HCC tissues compared with normal liver tissues, and its level was higher in HCC tissues with higher histological grade and advanced tumor stage. In addition, it was found that overexpression of miR-30a-5p significantly suppressed the tumor growth of HCC cells in nude mice. Taken together, the present study supports that miR-30a-5p inhibits the proliferation, invasion, and tumor growth of HCC cells, partly at least, by inhibition of FOXA1 expression, and therefore suggests that miR-30a-5p may serve as a potential candidate for HCC therapy.

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Section: Introductionmentioning

confidence: 99%

MicroRNA-30a-5p suppresses proliferation, invasion and tumor growth of hepatocellular cancer cells via targeting FOXA1

et al. 2017

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“…In pancreatic cancer, miR-138 overexpression reduced pancreatic cancer cell growth through directly targeting forkhead box C1 (30). In hepatocellular carcinoma, restoration of miR-138 expression suppressed cell viability and colony formation, and decreased tumor cell growth in xenograft nude mice by directly targeting cyclin D3 (36). Thus, re-expression of miR-138 in these human cancer types may be a new potential therapeutic approach.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑138 suppresses cell proliferation and invasion of renal cell carcinoma by directly targeting SOX9

Wang

Jin

2017

Oncol Lett

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Abstract. An accumulating number of studies have reported that the expression levels of microRNAs (miRNAs/miRs) are dysregulated in a variety of human cancer types, including renal cell carcinoma (RCC). miRNAs play essential functions in tumorigenesis and the progression of tumors by serving as oncogenes or tumor suppressors. Recently, the expression and functions of miR-138 have been studied in a number of human cancer types; however, its role in RCC remains poorly understood. In the present study, the results revealed that miR-138 was significantly downregulated in RCC cell lines and tissues, and that low expression levels of miR-138 were correlated with histological grade, tumor stage and lymph node metastasis. In functional studies, restoration of miR-138 expression inhibited cell proliferation and invasion of ACHN and A498 cells. In addition, SOX9 was validated as a direct target gene of miR-138 in RCC. SOX9 knockdown inhibited cell proliferation and invasion of RCC, with a similar effect to that induced by miR-138, rendering SOX9 a functional target of miR-138 in the disease. These findings indicate that miR-138 may present a novel target for therapeutic strategies in RCC.

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“…[42][43][44][45] However, there is currently no functional evidence of any physiopathological implication of miR-483-3p downregulation in these processes. Conversely, miR-483-3p is overexpressed in cancers associated with biallelic expression of its host gene IGF2 due to LOI of the IGF2/H19 locus.…”

Section: Discussionmentioning

confidence: 99%

CDC25A targeting by miR-483-3p decreases CCND–CDK4/6 assembly and contributes to cell cycle arrest

et al. 2013

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Disruption of contact inhibition and serum afflux that occur after a tissue injury activate cell cycle, which then stops when confluence is reached again. Although the events involved in cell cycle entry have been widely documented, those managing cell cycle exit have remained so far ill defined. We have identified that the final stage of wound closure is preceded in keratinocytes by a strong accumulation of miR-483-3p, which acts as a mandatory signal triggering cell cycle arrest when confluence is reached. Blocking miR-483-3p accumulation strongly delays cell cycle exit, maintains cells into a proliferative state and retards their differentiation program. Using two models of cell cycle synchronization (i.e. mechanical injury and serum addition), we show that an ectopic upregulation of miR-483-3p blocks cell cycle progression in early G1 phase. This arrest results from a direct targeting of the CDC25A phosphatase by miR-483-3p, which can be impeded using an anti-miRNA against miR-483-3p or a protector that blocks the complex formation between miR-483-3p and the 3 0 -untranslated region (UTR) of CDC25A transcript. We show that the miRNA-induced silencing of CDC25A increases the tyrosine phosphorylation status of CDK4/6 cyclin-dependent kinases which, in turn, abolishes CDK4/6 capacity to associate with D-type cyclins. This prevents CDK4/6 kinases' activation, impairs downstream events such as cyclin E stimulation and sequesters cells in early G1. We propose this new regulatory process of cyclin-CDK association as a general mechanism coupling miRNA-mediated CDC25A invalidation to CDK posttranscriptional modifications and cell cycle control.

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MiR-138 induces cell cycle arrest by targeting cyclin D3 in hepatocellular carcinoma

Cited by 192 publications

References 49 publications

MicroRNA-30a-5p suppresses proliferation, invasion and tumor growth of hepatocellular cancer cells via targeting FOXA1

MicroRNA-30a-5p suppresses proliferation, invasion and tumor growth of hepatocellular cancer cells via targeting FOXA1

MicroRNA‑138 suppresses cell proliferation and invasion of renal cell carcinoma by directly targeting SOX9

CDC25A targeting by miR-483-3p decreases CCND–CDK4/6 assembly and contributes to cell cycle arrest

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