Sp1-driven up-regulation of miR-19a decreases RHOB and promotes pancreatic cancer

Tan, Yulong; Yin, Han; Zhang, Heying; Fang, Jun; Zheng, Wei; Li, Dan; Li, Yue; Cao, Wei; Sun, Chengyi; Liang, Yunmei; Zeng, Juan; Zou, Huawei; Fu, Wei‐Neng; Yang, Xianghong

doi:10.18632/oncotarget.3975

Cited by 48 publications

(41 citation statements)

References 48 publications

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“…The results captured the imagination of the role miR‐19a‐3p plays in disease process of PC. According to Tan et al, higher levels of miR‐19a were found in PC tissues and miR‐19a was confirmed to have tumor‐promoting effect of stimulating cell proliferation, migration, invasion in vitro and tumor growth in vivo by targeting RHOB in PC . Besides PC, miR‐19a is also frequently overexpressed in tumor cells and acts as tumor‐promoting factor in other cancer types such as lung carcinoma, colorectal cancer, cervical carcinoma, and gastric cancer .…”

Section: Discussionmentioning

confidence: 99%

Identification of a six‐miRNA panel in serum benefiting pancreatic cancer diagnosis

et al. 2019

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Pancreatic cancer (PC) has posed a great health threat to a growing number of people all over the world. Detection of serum miRNAs, being sensitive, noninvasive, and easy to obtain, has a great potential of being a novel screening method for PC patients. In this study, we investigated miRNA expression levels in serum by qRT‐PCR. The study was divided into four phases: the screening, training, testing, and external validation stage. We firstly chose candidate miRNAs using Exiqon panels in the screening phase. Then, a total of 129 PC serum samples and 107 normal controls (NCs) were further analyzed in the following training and testing phases to identify differently expressed miRNAs. A cohort of 30 PC serum samples vs 30 NCs was used to confirm the diagnostic value of the identified miRNAs in the external validation phase. Moreover, miRNA expressions in additional 44 PC tumor tissue samples and the matched adjacent normal tissue samples as well as 32 pairs of serum‐derived exosomes samples were also further explored. As a result, we identified six significantly upregulated miRNAs in the serum of PC: let‐7b‐5p, miR‐192‐5p, miR‐19a‐3p, miR‐19b‐3p, miR‐223‐3p, and miR‐25‐3p. A six‐miRNA panel in serum was then established. The area under the receiver operating characteristic curves (AUC) for the panel was 0.910 for the combined training and testing phases, which showed higher diagnostic value than the individual miRNA. Prognostic value prediction using Cox's proportional hazards model and Kaplan‐Meier curves showed that increased serum miR‐19a‐3p was closely related to worse overall survival (OS). In addition, significant upregulation of miR‐192‐5p, miR‐19a‐3p, and miR‐19b‐3p was observed in both PC tissue and serum‐derived exosomes samples. In conclusion, we identified a six‐miRNA (let‐7b‐5p, miR‐192‐5p, miR‐19a‐3p, miR‐19b‐3p, miR‐223‐3p, and miR‐25‐3p) panel in the serum for PC early and noninvasive diagnosis.

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Section: Discussionmentioning

confidence: 99%

Identification of a six‐miRNA panel in serum benefiting pancreatic cancer diagnosis

et al. 2019

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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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“…MiR‐17‐92 cluster is regarded as the first miRNA cluster with oncogenic potential,15 the cluster includes 6 single mature miRNAs, miR‐19 has been supposed to be the key oncogenic miRNA among the six members of miR‐17‐92 cluster. MiR‐19 is located on chromosome 13 in c13orf25 16 and its expression is up‐regulated in bladder cancer, breast cancer, pancreatic cancer, gastric cancer and laryngeal squamous cell carcinoma 17, 18, 19, 20, 21. MiR‐19 promotes tumourigenesis by regulating target genes and related signalling pathways.…”

Section: Introductionmentioning

confidence: 99%

“…MiR-19 is located on chromosome 13 in c13orf25 16 and its expression is up-regulated in bladder cancer, breast cancer, pancreatic cancer, gastric cancer and laryngeal squamous cell carcinoma. [17][18][19][20][21] MiR-19 promotes tumourigenesis by regulating target genes and related signalling pathways. In human B-cell lymphomas, miR-19 promotes tumour cell survival by inhibiting PTEN directly and activating AKT/mTOR pathway.…”

Section: Introductionmentioning

confidence: 99%

The emerging role of miR‐19 in glioma

Wang

Zhang

Hao

et al. 2018

J Cellular Molecular Medi

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Glioma has been regarded as the most common, highly proliferative and invasive brain tumour. Advances in research of miRNAs in glioma are toward further understanding of the pathogenesis of glioma. MiR‐19, a member of miR‐17~92 cluster, was reported to play an oncogenic role in tumourigenesis. Here we review the identified data about the effect of miR‐19 on proliferation, apoptosis, migration and invasion of glioma cells, the target genes regulated by miR‐19, and correlation of miR‐19 with the sensitivity of glioma cells to chemotherapy and radiotherapy. It is concluded that miR‐19 plays an important role in the pathogenesis of glioma and can be a potential target for gene therapy of glioma.

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Sp1-driven up-regulation of miR-19a decreases RHOB and promotes pancreatic cancer

Cited by 48 publications

References 48 publications

Identification of a six‐miRNA panel in serum benefiting pancreatic cancer diagnosis

Identification of a six‐miRNA panel in serum benefiting pancreatic cancer diagnosis

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

The emerging role of miR‐19 in glioma

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