miR-451: Potential role as tumor suppressor of human hepatoma cell growth and invasion

Liu, Xuemin; Zhang, Xufeng; Xiang, Jun; Lv, Yi; Shi, Jing

doi:10.3892/ijo.2014.2446

Cited by 23 publications

(21 citation statements)

References 30 publications

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“…It was observed that restoration of miR-451 could significantly inhibit in vitro growth and in vivo tumorigenesis of HCC cells by inducing G 0 /G 1 arrest and apoptosis enhancement, which were consistent with the report by Li’ et al [ 23 ]. Likewise, another report reveals a prominent role of miR-451 as a tumor suppressor regulating HCC growth in a caspase-3-dependent manner [ 31 ]. Previously, we have shown that miR-451 significantly suppresses growth in NSCLC, and the tumor-suppressive effects of miR-451 are reported in other human cancers.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-451: epithelial-mesenchymal transition inhibitor and prognostic biomarker of hepatocelluar carcinoma

et al. 2015

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Increasing evidence indicates that dysregulation of microRNAs (miRNAs) plays critical roles in malignant transformation and tumor progression. Previously, we have shown that microRNA-451 (miR-451) inhibits growth, increases chemo- or radiosensitivity and reverses epithelial to mesenchymal transition (EMT) in lung cancer. However, the roles of miR-451 in hepatocelluar carcinoma (HCC) progression and metastasis are still largely unknown. Reduced miR-451 in HCC tissues was observed to be significantly correlated with advanced clinical stage, metastasis and worse disease-free or overall survival. Through gain- and loss-of function experiments, we demonstrated that miR-451 inhibited cell growth, induced G0/G1 arrest and promoted apoptosis in HCC cells. Importantly, miR-451 could inhibit the migration and invasion in vitro, as well as in vivo metastasis of HCC cells through regulating EMT process. Moreover, the oncogene c-Myc was identified as a direct and functional target of miR-451 in HCC cells. Knockdown of c-Myc phenocopied the effects of miR-451 on EMT and metastasis of HCC cells, whereas overexpression of c-Myc partially attenuated the functions of miR-451 restoration. Furthermore, miR-451 downregulation-induced c-Myc overexpression leads to the activation of Erk1/2 signaling, which induces acquisition of EMT phenotype through regulation of GSK-3β/snail/E-cadherin and the increased expression of MMPs family members in HCC cells. Collectively, these data demonstrated that miR-451 is a novel prognostic biomarker for HCC patients and that function as a potential metastasis inhibitor in HCC cells through activation of the Erk1/2 signaling, at least partially by targeting c-Myc. Thus, targeting miR-451/c-Myc/Erk1/2 axis may be a potential strategy for the treatment of metastatic HCC.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-451: epithelial-mesenchymal transition inhibitor and prognostic biomarker of hepatocelluar carcinoma

et al. 2015

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“…In glioma cells, mTOR (mammalian target of rapamycin), a highly conserved serine/threonine kinase found in all eukaryotic cells, is considered to be a central regulator of cell growth (9). In contrast, Ras-related C3 botulinum toxin substrate 1 (Rac1), a member of the Rho family of GTPases, promotes cell migration by regulating actin polymerization at the front of migrating cells and induces the formation of membrane ruffles and lamellipodia (10,11). It is reasonable to assume that the switching of cellular phenotype from proliferation to migration might be alternatively regulated by mTOR or Rac1 activation.…”

Section: Introductionmentioning

confidence: 99%

The role of miR-451 in the switching between proliferation and migration in malignant glioma cells: AMPK signaling, mTOR modulation and Rac1 activation required

Zhao

Wang

et al. 2017

International Journal of Oncology

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Glioblastoma multiforme (GBM), WHO grade IV astrocytoma, is the most common primary neoplasm of the central nervous system (CNS) and has the highest malignancy and mortality rates. The invasive nature of GBM complicates surgical resection and restricts chemotherapeutic access, contributing to poor patient prognosis. The migration of tumor cells is closely related to the tumor cell proliferation. The acquisition of migratory capability, in addition to intracellular factors, is proposed to be a crucial mechanism during the progression of invasion. Using qRT-PCR analysis, we determined that the expression of miR-451 in glioma tissue was lower than in control brain tissue, especially in the central portions of the tumor. In glioma cell lines, we found that decreased miR-451 expression suppressed tumor cell proliferation but enhanced migration with a concomitant low level of CAB39/AMPK/mTOR pathway activation and high level of Rac1/cofilin pathway activation, respectively. Notably, the effect of miR-451 on cytological behavior and on the activation of mTOR and Rac1 was limited when AMPKα1 expression was knocked-down with a synthetic shRNA. We suggest that the glioma microenvironment results in heterogeneity of miR-451 expression. Our data indicated that miR-451 relays environmental signals by upregulating the activity of AMPK signaling, thereby modulating the activation of mTOR and Rac1/cofilin which, in turn, play key roles in glioma cell proliferation and migration, respectively. Our results highlight the need to consider opposing roles of a therapeutic target which, while suppressing tumor cell proliferation, could also promote cell infiltration.

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“…It has been found to be expressed in several human tissues and has a high level of expression in foetuses, compared with adults. Previous evidence has indicated that miR-451 can function as a tumour suppressor in nasopharyngeal carcinoma (14), hepatocellular carcinoma (15,16) and bladder cancer (17). Despite these previous findings concerning miR-451 and its important roles in carcinogenesis, there have been no reports to date regarding an association between miR-451 and NB.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-451 inhibits neuroblastoma proliferation, invasion and migration by targeting macrophage migration inhibitory factor

Zhou

Hao

2016

Molecular Medicine Reports

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Neuroblastoma (NB) is the most prevalent type of extracranial solid tumour in young children. To improve current understanding of the mechanisms, which modulate cancer cell proliferation, invasion and migration, investigations have focused on microRNAs (miRs), a class of small non‑coding RNAs, which post‑transcriptionally regulate gene expression during various crucial cell processes. The present study aimed to investigate the role of miR‑451 in NB. Human NB tissue and adjacent normal tissue were surgically removed, and the expression of miR‑451, and development and pathological characteristics of NB were investigated. The expression of miR‑451 was reduced in the NB tissue, compared with that in the adjacent tissue, and correlations between the reduction in miR‑451 and unfavourable variables included tumour size (P=0.0081), differentiation (P=0.0217), lymph node metastasis (P=0.0489), tumour‑node‑metastasis stage (0.0220) and distant metastases (P=0.0201). Transfection of the SK‑N‑SH and GI‑LA‑N NB cell lines with miR‑451 inhibited cell growth, invasion and migration. Furthermore, the present study demonstrated that macrophage migration inhibitory factor (MIF) was regulated directly by miR‑451 and was a critical mediator of the biological effects of miR‑451 in NB. The re‑expression of MIF markedly reversed the carcinogenic inhibitory property of miR‑451. These data provide a more detailed understanding of the essential role of miR‑451 in NB, which relies on regulation of the expression of MIF.

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miR-451: Potential role as tumor suppressor of human hepatoma cell growth and invasion

Cited by 23 publications

References 30 publications

MicroRNA-451: epithelial-mesenchymal transition inhibitor and prognostic biomarker of hepatocelluar carcinoma

MicroRNA-451: epithelial-mesenchymal transition inhibitor and prognostic biomarker of hepatocelluar carcinoma

The role of miR-451 in the switching between proliferation and migration in malignant glioma cells: AMPK signaling, mTOR modulation and Rac1 activation required

MicroRNA-451 inhibits neuroblastoma proliferation, invasion and migration by targeting macrophage migration inhibitory factor

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