Insulin receptor substrate-1 and Golgi phosphoprotein 3 are downstream targets of miR-126 in esophageal squamous cell carcinoma

Li, Haomiao; Meng, Fanyu; Ma, Jun; Yu, Yonghao; Hua, Xionghuai; Qin, Jianjun; Li, Yin

doi:10.3892/or.2014.3327

Cited by 26 publications

(25 citation statements)

References 34 publications

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“…miRNAs promote mRNA degradation by inhibiting translation upon binding to the 3'-untranslated region (3'-UTR) of their target mRNA (12). Complementary binding of an miRNA and mRNA is not exclusive; a single miRNA can target hundreds of mRNAs, which was demonstrated in the present study and a single mRNA can be affected by multiple miRNAs (13)(14)(15)(16)(17). Consequently, miRNAs can act as tumor suppressors or possibly oncogenes depending on the target mRNAs (18,19).…”

Section: Introductionmentioning

confidence: 52%

Screening of differential microRNA expression in gastric signet ring cell carcinoma and gastric adenocarcinoma and target gene prediction

et al. 2015

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Gastric signet ring cell carcinoma (GSRCC) is a unique pathological type of gastric carcinoma that is extremely invasive and has a poor prognosis after diagnosis. The expression of microRNAs has been closely linked to the carcinogenesis of gastric cancer and has been considered as a powerful prognostic marker. Distinctive expression of miRNAs in GSRCC was investigated in the present study. Samples of GSRCC were compared to that of intestinal gastric adenocarcinoma using Agilent microarray technique, and two differentially expressed miRNAs were identified, hsa-miR-665 and hsa-miR‑95. qRT-PCR verification showed downregulation of both miRNAs in signet ring cell carcinoma and upregulation in gastric adenocarcinoma, which was not consistent with the results obtained by the microarray. Target gene prediction using online databases conferred two strong candidate genes, GLI2 and PLCG1. GO/KO analysis of these two genes showed close correlations with carcinogenesis and chemoresistance. It was concluded that hsa-miR-665 and hsa-miR-95 were downregulated in GSRCC but upregulated in intestinal gastric adenocarcinoma, and the relatively differential expression of the miRNAs negatively controlling their target genes could be closely related to the high invasive metastasis and chemoresistance of GSRCC.

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Section: Introductionmentioning

confidence: 52%

Screening of differential microRNA expression in gastric signet ring cell carcinoma and gastric adenocarcinoma and target gene prediction

et al. 2015

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“…ii) If other signaling pathways or transcription factors, including NF-κB and AP-1 were associated the biological effect of miR-126, further studies are required to investigate their underlying mechanisms and cascade reactions. iii) Although certain targets of miR-126 were reported in different cell types and disease models, including EGFL7 (29), pik3r2 (30), ROCK1 (31), IRS-1 and GOLPH3 (32), to the best of our knowledge, Spred1 was reported as a direct target of miR-126 and was associated with MC activation (11). The present study focused on the direct effect of miR-126 on MC degranulation and its preliminary molecular mechanisms.…”

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confidence: 86%

MicroRNA‑126 accelerates IgE‑mediated mast cell degranulation associated with the PI3K/Akt signaling pathway by promoting Ca2+ influx

et al. 2018

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Mast cells (MCs) have been reported to serve a crucial role in allergic diseases, including asthma, allergic rhinitis and anaphylaxis. A previous study revealed that microRNA-126 (miR-126) was associated with airway hyperresponsiveness induced by house dust mites, however the molecular mechanisms were unclear. The present study aimed to investigate the effect of miR-126 on immunoglobulin E (IgE)-regulated MC degranulation and explore its underlying mechanisms. miR-126 expression was quantified using a rat model and in rat peritoneal mast cells (RPMCs). Overexpression or downregulation of miR-126 was established by transfection with miR-126 mimics or miR-126 inhibitors and MC degranulation was subsequently evaluated. The effect of miR-126 on protein kinase B (Akt) and phosphorylated Akt protein expression was examined by western blot analysis. The phosphoinositide 3-kinase (PI3K) inhibitor (LY294002) was used to determine the role of the PI3K/Akt signaling pathway. In addition, cytosolic calcium (Ca) levels were measured by a fura-2 assay. The results demonstrated that miR-126 expression was upregulated in the ear tissues of rats with allergic contact dermatitis and IgE-activated MCs. The overexpression of miR-126 in RPMCs was established following miR-126 mimic transfection. The release of β-hexosaminidase and histamine, markers of MC degranulation, were significantly increased in cells with miR-126 overexpression. The phosphorylation of Akt was significantly increased following transfection with miR-126 mimics in stimulated cells, however the signaling activation was abrogated by LY294002. In addition, Ca influx was significantly promoted in stimulated RPMCs overexpressing miR-126. These results indicate that miR-126 accelerated IgE-mediated MC degranulation associated with the PI3K/Akt signaling pathway by promoting Ca influx. This suggests that miR-126 may be a promising therapeutic target for the treatment of allergic skin diseases.

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“…A previous study reported that miR-126 was able to regulate PTPN9 in the hematopoietic differentiation of human embryonic stem cells at the post-transcriptional level (29). Frequently described as a tumor suppressor in a number of studies, miR-126 was observed to be downregulated in ESCC tissues and cell lines (32,37–39). However, the interaction between miR-126 and PTPN9 in the process of ESCC remains to be established.…”

Section: Discussionmentioning

confidence: 99%

“…Immunohistochemistry was performed as previously described (32). Rabbit anti-human PTPN9 antibody (dilution, 1:50; cat.…”

Section: Methodsmentioning

confidence: 99%

PTPN9 promotes cell proliferation and invasion in Eca109 cells and is negatively regulated by microRNA-126

Zhu

et al. 2017

Oncology Letters

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Protein tyrosine phosphatase non-receptor type 9 (PTPN9), also named PTP-MEG2, is an important member of the protein tyrosine phosphatase family that is involved in variety of human diseases. However, the role of PTPN9 in esophageal squamous cell carcinoma (ESCC) remains to be established. The present evaluated the potential effect and underlying mechanism of action of PTPN9 in ESCC. Immunohistochemistry was performed to detect PTPN9 protein expression in 84 ESCC tumor specimens and 30 normal esophageal tissues. The association between positive expression of PTPN9 and clinicopathological features and prognosis was analyzed. The prognostic role of PTPN9 was further investigated using multivariate regression analysis. PTPN9-small interfering RNA and microRNA (miR-126)-mimics were transfected into Eca109 cells to construct PTPN9 silencing and an miR-126 ectopic expression cell model. Reverse transcription-quantitative polymerase chain reaction, western blot analysis, cell counting kit-8, Transwell assays and flow cytometry were used to investigate the role of PTPN9 in the process of ESCC progression and its potential downstream signaling pathway. Immunohistochemical analysis revealed that PTPN9 was upregulated in ESCC tumor specimens compared with normal esophageal tissues. The χ2 test indicated that positive expression of PTPN9 was correlated with tumor node metastasis stage, tumor classification and node classification. Patients with PTPN9 positive expression had shorter survival time, compared with those that were PTPN9 negative. Multivariate regression analysis with the Cox proportional hazards regression model revealed that PTPN9 expression was a prognostic factor of overall survival for patients with ESCC. Using RNA interference, the present study demonstrated that knockdown of PTPN9 significantly suppressed cell proliferation and invasion in Eca109. Additionally, it was hypothesized that miR-126, described as a tumor suppressor in ESCC, may act at least in part via its inhibition of PTPN9 at the post-transcriptional level. To the best of our knowledge, this is the first study to demonstrate that PTPN9 is overexpressed in ESCC and associated with poor survival, and may therefore be important in the pathogenesis of ESCC.

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Insulin receptor substrate-1 and Golgi phosphoprotein 3 are downstream targets of miR-126 in esophageal squamous cell carcinoma

Cited by 26 publications

References 34 publications

Screening of differential microRNA expression in gastric signet ring cell carcinoma and gastric adenocarcinoma and target gene prediction

Screening of differential microRNA expression in gastric signet ring cell carcinoma and gastric adenocarcinoma and target gene prediction

MicroRNA‑126 accelerates IgE‑mediated mast cell degranulation associated with the PI3K/Akt signaling pathway by promoting Ca2+ influx

PTPN9 promotes cell proliferation and invasion in Eca109 cells and is negatively regulated by microRNA-126

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