miR-221 increases osteosarcoma cell proliferation, invasion and migration partly through the downregulation of PTEN

Jun, Zhu; Fan, Li; Wu, Quanming; Liu, Xiancheng

doi:10.3892/ijmm.2015.2352

Cited by 26 publications

(19 citation statements)

References 40 publications

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“…Phosphatase and tensin homologue (PTEN), located on chromosome10q23, has been reported to be downregulated in OS tissues and cell lines, and low PTEN expression was associated with poor prognosis [28][29][30]. In addition, overexpression of PTEN significantly inhibits OS cell proliferation, migration, and invasion, and induces cell apoptosis [31,32]. Of note, the regulatory mechanism between FER1L4 and PTEN has been revealed in endometrial carcinoma [15] and gastric cancer [12].…”

Section: Discussionmentioning

confidence: 99%

Long Noncoding RNA FER1L4 Suppresses Tumorigenesis by Regulating the Expression of PTEN Targeting miR-18a-5p in Osteosarcoma

Fei

Zhang

Liu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Novel long non-coding RNA Fer-1-like protein 4 (FER1L4) has been reported to play crucial regulatory roles in tumor progression. However, its clinical significance and biological role in osteosarcoma (OS) is completely unknown. The aim of the present study was to investigate the role of FER1L4 in OS progression and the underlying mechanism. Methods: We analyzed the expression levels of FER1L4 in tissues of OS patients and cell lines via quantitative RT-PCR (qRT-PCR). The effect of FER1L4 on cell proliferation, colony formation, migration and invasion was analyzed by cell counting kit-8 (CCK-8), colony formation, wound healing and transwell invasion assay, respectively. Novel targets of FER1L4 were selected through a bioinformatics soft and confirmed using a dual-luciferase reporter system and qRT-PCR. To detect the role of FER1L4 in vivo tumorigenesis, tumor xenografts were created. Results: We found that the expression of FER1L4 was significantly downregulated in OS tissues and cell lines; moreover, low expression of FER1L4 was associated with advanced tumor-nude-metastasis (TNM) stage, lymph node metastases, and poor overall survival. Functional assays showed that upregulation of FER1L4 significantly inhibited OS cell proliferation, colony formation, migration, and invasion in vitro, as well as suppressed tumor growth in vivo. Assays performed to determine the underlying mechanism, indicated that FER1L4 interacted directly with miR-18a-5p. Subsequently, we found that FER1L4 significantly increased PTEN expression, a known target of miR-18a-5p, in OS cells. Furthermore, PTEN was found to be down-regulated, and positively correlated with FER1L4 in OS tissues. Conclusion: These findings suggest that FER1L4, acting as a competing endogenous RNA (ceRNA) of miR-18a-5p, exerts its anti-cancer role by modulating the expression of PTEN. Thus, FER1L4 may be a novel target for the prevention and treatment of OS.

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Section: Discussionmentioning

confidence: 99%

Long Noncoding RNA FER1L4 Suppresses Tumorigenesis by Regulating the Expression of PTEN Targeting miR-18a-5p in Osteosarcoma

Fei

Zhang

Liu

et al. 2018

Cell Physiol Biochem

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“…Furthermore, miR-9 has been shown to be activated by HPV leading to increased cell motility [53] and to be involved in the pathways regulating metastasis [54]. Upregulated miR-31, miR-221, and miR-21 were selected for confirmation from the group of miRNAs specific for HPV-independent tumors including HNC as playing a role in increasing cell proliferation, invasion, and migration [55–58], participating in regulation of epithelial-mesenchymal transition (EMT), or having a prognostic impact [59, 60]. Further choices were miR-34a, specific for HPV-negative tumors, a tumor suppressor whose downregulation has been shown in a number of tumor types including HNC [61, 62], as well as miR-16, the inhibition of which promotes cell proliferation, migration, invasion, and EMT and contributes to tumor progression [63].…”

Section: Discussionmentioning

confidence: 99%

Comparison of the miRNA expression profiles in fresh frozen and formalin-fixed paraffin-embedded tonsillar tumors

et al. 2017

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MicroRNAs are considered as promising prognostic and diagnostic biomarkers of human cancer since their profiles differ between tumor types. Most of the tumor profiling studies were performed on rarely available fresh frozen (FF) samples. Alternatively, archived formalin-fixed paraffin-embedded (FFPE) tissue samples are also well applicable to larger-scale retrospective miRNA profiling studies. The aim of this study was to perform systematic comparison of the miRNA expression profiles between FF and macrodissected FFPE tonsillar tumors using the TaqMan Low Density Array system, with the data processed by different software programs and two types of normalization methods. We observed a marked correlation between the miRNA expression profiles of paired FF and FFPE samples; however, only 27-38% of the differentially deregulated miRNAs overlapped between the two source systems. The comparison of the results with regard to the distinct modes of data normalization revealed an overlap in 58–67% of differentially expressed miRNAs, with no influence of the choice of software platform. Our study highlights the fact that for an accurate comparison of the miRNA expression profiles from published studies, it is important to use the same type of clinical material and to test and select the best-performing normalization method for data analysis.

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“…MiRNAs/PTEN axis has been proved to regulate the cell growth and apoptosis in multiple cancers. 33,34 In this study, we demonstrate that the gene of PTEN, which is downregulated in OS stem cells, is the target of miR-19a. Our data prove that knockdown of miR-19a increases the expression of PTEN in OS stem cells.…”

Section: Discussionmentioning

confidence: 99%

MiR-19a regulates the cell growth and apoptosis of osteosarcoma stem cells by targeting PTEN

et al. 2017

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MicroRNAs are small, endogenous, and non-coding RNAs that play important regulatory roles in multiple biological processes in cancers. Recent evidence has indicated that miR-19a participates in the cancer tumorigenic progression. However, the functional roles of miR-19a in cancer stem cells are still unclear. As the cancer stem cells are considered to be responsible for the tumor recurrence and treatment failure in osteosarcoma, the aim of this study is to investigate the molecular mechanism of miR-19a underlying osteosarcoma tumorigenesis. In this study, we observed significant upregulation of miR-19a in osteosarcoma patients' tumor tissues as well as the osteosarcoma cell lines in vitro. We showed that knockdown of miR-19a by its antisense oligonucleotide (anti-miR-19a) significantly decreased the population of cancer stem cells in osteosarcoma cell lines. Furthermore, we found the miR-19a regulated the cell proliferation, migration, and viability in the human osteosarcoma-cancer stem cells. The gene of phosphatase and tensin homolog deleted on chromosome 10, which is an important tumor suppressor, was found to be directly regulated by miR-19a in human osteosarcoma-cancer stem cells. We demonstrated that knockdown of miR-19a increased the expression of phosphatase and tensin homolog deleted on chromosome 10. As the anti-miR-19a inhibited the phosphatidylinositol 3-kinase/AKT pathway and induced apoptosis of human osteosarcoma-cancer stem cells, the phosphatase and tensin homolog deleted on chromosome 10 small interfering RNA inhibited the effect of it. Meanwhile, the phosphatase and tensin homolog deleted on chromosome 10 small interfering RNA also abolished the effect of anti-miR-19a on inhibiting the cell proliferation, migration, and viability in the human osteosarcoma-cancer stem cells. In conclusion, our findings demonstrated that dysregulation of miR-19a plays critical roles in the osteosarcoma stem cells, at least in part via targeting the phosphatase and tensin homolog deleted on chromosome 10. Knockdown of miR-19a may represent a potential strategy for the osteosarcoma treatment.

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miR-221 increases osteosarcoma cell proliferation, invasion and migration partly through the downregulation of PTEN

Cited by 26 publications

References 40 publications

Long Noncoding RNA FER1L4 Suppresses Tumorigenesis by Regulating the Expression of PTEN Targeting miR-18a-5p in Osteosarcoma

Long Noncoding RNA FER1L4 Suppresses Tumorigenesis by Regulating the Expression of PTEN Targeting miR-18a-5p in Osteosarcoma

Comparison of the miRNA expression profiles in fresh frozen and formalin-fixed paraffin-embedded tonsillar tumors

MiR-19a regulates the cell growth and apoptosis of osteosarcoma stem cells by targeting PTEN

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