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

Zhao, Di; Chen, Youbin; Shun-liang, Chen; Zheng, Cuifang; Hu, Jun; Luo, Shaowei

doi:10.1177/1010428317705341

Cited by 32 publications

(19 citation statements)

References 32 publications

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“…23,24 They have the potential to regulate various critical biological processes including proliferation, migration and apoptosis of different kind of cancer cells. 25,26 Previous studies have indicated that many miRNAs, such as miR-19a, 27 miR-610, 28 CXCR4 is a well-studied G-protein coupled chemokine receptor and commonly expressed on lots of cell types including osteosarcoma cells. 34 The binding of SDF-1 to CXCR4 results in divergent downstream signaling pathways that mediate cell proliferation, migration and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

CXCR4‐mediated osteosarcoma growth and pulmonary metastasis is suppressed by MicroRNA‐613

et al. 2018

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Osteosarcoma is the most common primary bone malignancy. Recently, studies showed chemokine receptor 4 (CXCR4) played a critical role in osteosarcoma. However, the regulation of CXCR4 is not fully understood. microRNAs are short, non‐coding RNAs that play an important roles in post‐transcriptional regulation of gene expression in a variety of diseases including osteosarcoma. miR‐613 is a newly discovered miRNA and has been reported to function as a tumor suppressor in many cancers. In this study, we confirmed that both Stromal Cell‐Derived Factor (SDF‐1) and CXCR4 could be prognostic markers for osteosarcoma. Meanwhile this study found that SDF‐1/CXCR4 pathway regulated osteosarcoma cells proliferation, migration and reduced apoptosis. Besides, we demonstrated that miR‐613 was significantly downregulated in osteosarcoma patients. Elevated expression of miR‐613 directly suppressed CXCR4 expression and then decreased the proliferation, migration and induced apoptosis of osteosarcoma cells. Moreover, our study found that CXCR4 promoted the development of lung metastases and inhibition of CXCR4 by miR‐613 reduced lung metastases. These data indicated that CXCR4 mediated osteosarcoma cell growth and lung metastases and this effect can be suppressed by miR‐613 through directly downregulating CXCR4.

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Section: Discussionmentioning

confidence: 99%

CXCR4‐mediated osteosarcoma growth and pulmonary metastasis is suppressed by MicroRNA‐613

et al. 2018

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“…To our knowledge, the present study is the first to provide evidence that PITX1 expression is modulated through miR-19a-3p in GC. miR-19a is frequently overexpressed, promotes cell proliferation and the epithelial to mesenchymal transition, and inhibits cell apoptosis in lung carcinoma [36,37], osteosarcoma stem cells [38], colorectal cancer [39][40][41][42], cell renal cell carcinoma [43], oral squamous cell carcinoma [44], hepatocellular carcinoma cells [45], pancreatic cancer [46], GC [47,48], cholangiocarcinoma [49], breast cancer [50], bladder cancer [51], medulloblastoma [52], and cervical carcinoma [53]. Our findings are consistent with these data because they provide evidence that miR19a is a key regulator of the multistep processes of cancer development.…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

Downregulated PITX1 Modulated by MiR-19a-3p Promotes Cell Malignancy and Predicts a Poor Prognosis of Gastric Cancer by Affecting Transcriptionally Activated PDCD5

Qiao

Gong

Song

et al. 2018

Cell Physiol Biochem

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Background/Aims: PITX1 has been identified as a potential tumor-suppressor gene in several malignant tumors. The molecular mechanism underlying PITX1, particularly its function as a transcription factor regulating gene expression during tumorigenesis, is still poorly understood. Methods: The expression level and location of PITX1 were determined by quantitative reverse transcription PCR (qRT-PCR) and immunohistochemical staining in gastric cancer (GC). The effect of PITX1 on the GC cell proliferation and tumorigenesis was analyzed in vitro and in vivo. To explore how PITX1 suppresses cell proliferation, we used PITX1-ChIP-sequencing to measure genome-wide binding sites of PITX1 and assessed global function associations based on its putative target genes. ChIP-PCR, electrophoretic mobility shift assay, and promoter reporter assays examined whether PITX1 bound to PDCD5 and regulated its expression. The function of PDCD5 in GC cell apoptosis was further examined in vitro and in vivo. The relationship between the PITX1 protein level and GC patient prognosis was evaluated by the Kaplan-Meier estimator. Meanwhile, the expression level of miR-19a-3p, which is related to PITX1, was also detected by luciferase reporter assay, qRT-PCR, and western blotting. Results: The expression level of PITX1 was decreased in GC tissues and cell lines. Elevated PITX1 expression significantly suppressed the cell proliferation of GC cells and tumorigenesis in vitro and in vivo. PITX1 knockdown blocked its inhibition of GC cell proliferation. PITX1 bound to whole genomewide sites, with these targets enriched on genes with functions mainly related to cell growth and apoptosis. PITX1 bound to PDCD5, an apoptosis-related gene, during tumorigenesis, and cis-regulated PDCD5 expression. Increased PDCD5 expression in GC cells not only induced GC cell apoptosis, but also suppressed GC cell growth in vitro and in vivo. Moreover, PITX1 expression was regulated by miR-19a-3p. More importantly, a decreased level of PITX1 protein was correlated with poor GC patient prognosis. Conclusion: Decreased expression of PITX1 predicts shorter overall survival in GC patients. As a transcriptional activator, PITX1 regulates apoptosis-related genes, including PDCD5, during gastric carcinogenesis. These data indicate PDCD5 to be a novel and feasible therapeutic target for GC.

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“…To find the target of miR-19a-3p, we used Targetscan, miRanda to predict potential target mRNAs, such as KBTBD8, ZMYND11, targeting PTEN in osteosarcoma stem cells and hepatocellular carcinoma. 12,13 Moreover, we found that the expression levels of PTEN mRNA were obviously up-regulated when overexpressed SLC25A5-AS1 in SGC-7901 and BGC-823 cells ( Figure 7A,B).…”

Section: Slc25a5-as1 Inhibits Cell Growth and Promotes Apoptosis VImentioning

confidence: 94%

Down‐regulated lncRNA SLC25A5‐AS1 facilitates cell growth and inhibits apoptosis via miR‐19a‐3p/PTEN/PI3K/AKT signalling pathway in gastric cancer

Yan

Wang

et al. 2019

J Cellular Molecular Medi

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Mounting evidence has illustrated the vital roles of long non‐coding RNAs (lncRNAs in gastric cancer (GC). Nevertheless, the majority of their roles and mechanisms in GC are still largely unknown. In this study, we investigate the roles of lncRNA SLC25A5‐AS1 on tumourigenesis and explore its potential mechanisms in GC. The results showed that the expressions of SLC25A5‐AS1 in GC were significantly lower than that of adjacent normal tissues, which were significantly associated with tumour size, TNM stage and lymph node metastasis. Moreover, SLC25A5‐AS1 could inhibit GC cell proliferation, induce G1/G1 cell cycle arrest and cell apoptosis in vitro, as well as GC growth in vivo. Dual‐luciferase reporter assay confirmed the direct interaction between SLC25A5‐AS1 and miR‐19a‐3p, rescue experiment showed that co‐transfection miR‐19a‐3p mimics and pcDNA‐SLC25A5‐AS1 could partially restore the ability of GC cell proliferation and the inhibition of cell apoptosis. The mechanism analyses further found that SLC25A5‐AS1 might act as a competing endogenous RNAs (ceRNA), which was involved in the derepression of PTEN expression, a target gene of miR‐19a‐3p, and regulate malignant phenotype via PI3K/AKT signalling pathway in GC. Taken together, this study indicated that SLC25A5‐AS1 was down‐regulated in GC and functioned as a suppressor in the progression of GC. Moreover, it could act as a ceRNA to regulate cellular behaviours via miR‐19a‐3p/PTEN/PI3K/AKT signalling pathway. Thus, SLC25A5‐AS1 might be served as a potential target for cancer therapeutics in GC.

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

Cited by 32 publications

References 32 publications

CXCR4‐mediated osteosarcoma growth and pulmonary metastasis is suppressed by MicroRNA‐613

CXCR4‐mediated osteosarcoma growth and pulmonary metastasis is suppressed by MicroRNA‐613

Downregulated PITX1 Modulated by MiR-19a-3p Promotes Cell Malignancy and Predicts a Poor Prognosis of Gastric Cancer by Affecting Transcriptionally Activated PDCD5

Down‐regulated lncRNA SLC25A5‐AS1 facilitates cell growth and inhibits apoptosis via miR‐19a‐3p/PTEN/PI3K/AKT signalling pathway in gastric cancer

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