Oncogenic miR-19a and miR-19b co-regulate tumor suppressor MTUS1 to promote cell proliferation and migration in lung cancer

Gu, Yuanyuan; Liu, Shuoxin; Zhang, Xiaodan; Chen, Guimin; Liang, Hongwei; Yu, Mengchao; Liao, Zhicong; Zhou, Yong; Zhang, Chenyu; Wang, Tao; Wang, Chen; Zhang, Junfeng; Chen, Xi

doi:10.1007/s13238-017-0393-7

Cited by 54 publications

(47 citation statements)

References 36 publications

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“…MiR‐19a was reported to significantly regulate cell proliferation and migration. miR‐19a‐3p inhibits invasion, migration, and bone metastasis in prostate cancer, while in lung cancer, miR‐19a promotes cell proliferation and migration . miR‐19a‐3p also regulates the viability, migration, and invasion of trophoblast cells, because the overexpression of miR‐19a‐3p attenuated the inhibition of the cell viability, migration, and invasion under hypoxemia.…”

Section: Discussionmentioning

confidence: 99%

Potential regulatory network in the PSG10P/miR‐19a‐3p/IL1RAP pathway is possibly involved in preeclampsia pathogenesis

Wang

Xue

2018

J Cellular Molecular Medi

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Preeclampsia (PE), a pregnancy‐specific disorder, is a leading cause of perinatal maternal‐fetal mortality and morbidity. Impaired cell migration and invasion of trophoblastic cells and an imbalanced systemic maternal inflammatory response have been proposed as potential mechanisms of PE pathogenesis. Comparative analysis between PE placentas and normal placentas profiled differentially expressed miRNAs, lncRNAs, and mRNAs, including miR‐19a‐3p (miRNA), PSG10P (lncRNA), and IL1RAP (mRNA). This study was conducted to investigate their potential roles in PE pathogenesis. The expression of miR‐19a‐3p, PSG10P, and IL1RAP was examined in PE and normal placentas using RT‐qPCR. An in vitro experiment was performed in human trophoblast HET8/SVneo and TEV‐1 cells cultured in normoxic and hypoxic conditions. MiR‐19a‐3p targets were identified using Targetscan, miRanda, and PicTar analysis as well as luciferase reporter assays. The mouse model of PE was conducted using sFlt‐1 for in vivo tests. Lower levels of miR‐19a‐3p, but higher levels of PSG10P and IL1RAP were observed in PE placentas and the trophoblast cells in hypoxia. Luciferase reporter assays confirmed that PSG10P and IL1RAP were both direct targets of miR‐19a‐3p. Exposure to hypoxia inhibited cell viability, migration, and invasion of HET8/SVneo and TEV‐1 cells. Knocking out PSG10P and IL1RAP or overexpressing miR‐19a‐3p rescued the inhibition caused by hypoxia. In vivo experiments showed that IL1RAP promoted the expression of caspase‐3, a key apoptosis enzyme, but inhibited MMP9, which is responsible for degrading the extracellular matrix, suggesting a significant role of IL1RAP in cell proliferation, migration, and invasion. miR‐19a‐3p, PSG10P, and IL1RAP were all found to be involved in PE pathogenesis. With a common targeting region in their sequences, a regulatory network in the PSG10P/miR‐19a‐3p/IL1RAP pathway may contribute to PE pathogenesis during pregnancy.

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Section: Discussionmentioning

confidence: 99%

Potential regulatory network in the PSG10P/miR‐19a‐3p/IL1RAP pathway is possibly involved in preeclampsia pathogenesis

Wang

Xue

2018

J Cellular Molecular Medi

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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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“…4 Accumulating evidence suggested that miRNAs play important roles in the initiation and progression of various human cancers including ovarian cancer. 5,6 miR-19a-3p is a member of the miR-17 to 92 clusters, its expression is frequently dysregulated and which is closely associated with proliferation, apoptosis, metastasis, and chemoresistance of various malignant tumors such as gastric cancer, 7,8 pancreatic cancer, 9 liver cancer, 10 lung cancer 11,12 and breast cancer. 13,14 It has been reported that miR-19a was highly expressed in ovarian cancer tissues and cell lines, and it promotes the growth of ovarian cancer cells.…”

Section: Introductionmentioning

confidence: 99%

The NF‐κB‐modulated miR‐19a‐3p enhances malignancy of human ovarian cancer cells through inhibition of IGFBP‐3 expression

Bai

Cui

et al. 2019

Molecular Carcinogenesis

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Ovarian cancer is the most lethal gynecologic malignancy due to the lack of symptoms until advanced stages, and new diagnosis and treatment strategy is in urgent need. In this study, we found higher expression of miR‐19a‐3p in ovarian cancer tissues compared with that in the adjacent normal tissues. By chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assay (EMSA) analysis, we showed that nuclear factor‐kappaB (NF‐κB) binds to the promoter of miR‐19a‐3p, leading to reduced expression in ovarian cancer cells. Further study indicated that miR‐19a‐3p inhibits the expression of insulin‐like growth factor binding protein‐3 (IGFBP‐3), resulting in enhanced growth and migration of ovarian cancer cells in vitro and tumor growth in vivo. These results showed that miR‐19a‐3p enhances the oncogenesis of ovarian cancer through inhibition of IGFBP‐3 expression, and which can be inhibited by NF‐κB, suggesting an NF‐κB/miR‐19a‐3p/IGFBP‐3 pathway in the oncogenesis of ovarian cancer, which expands our understanding of ovarian cancer and they may contribute to the development of new diagnosis and treatment of ovarian cancer.

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Oncogenic miR-19a and miR-19b co-regulate tumor suppressor MTUS1 to promote cell proliferation and migration in lung cancer

Cited by 54 publications

References 36 publications

Potential regulatory network in the PSG10P/miR‐19a‐3p/IL1RAP pathway is possibly involved in preeclampsia pathogenesis

Potential regulatory network in the PSG10P/miR‐19a‐3p/IL1RAP pathway is possibly involved in preeclampsia pathogenesis

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

The NF‐κB‐modulated miR‐19a‐3p enhances malignancy of human ovarian cancer cells through inhibition of IGFBP‐3 expression

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