MiR-758-3p suppresses proliferation, migration and invasion of hepatocellular carcinoma cells via targeting MDM2 and mTOR

Jiang, Dan; Cho, William C.; Li, Zhenhao; Xu, Xiangrong; Qu, Yuliang; Jiang, Zhongjia; Guo, Le; Xu, Guofeng

doi:10.1016/j.biopha.2017.10.004

Cited by 47 publications

(44 citation statements)

References 32 publications

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“…Many studies have shown that the activation of PI3 K/Akt signaling pathway is involved in promoting the proliferation of various cells, such as HC11 cell (Meng, Yuan, et al, 2017;Meng, Zhang, et al, 2017), human melanoma cells (De Cicco et al, 2016), and gliomas (Jiang et al, 2015). In agreement with these observations, we found the PI3 K/Akt signaling pathway was activated by low concentration The mTOR signaling pathway has also been involved in regulating the proliferation of different cells, including hepatocellular carcinoma cells (Jiang et al, 2017), vascular smooth muscle cells (Pan et al, 2017), and bovine mammary epithelial cells . In agreement, we found that mTOR signaling pathway was activated or inhibited in response to the low or high concentration of NaHS, respectively.…”

Section: Discussionsupporting

confidence: 88%

“…The mTOR signaling pathway has also been involved in regulating the proliferation of different cells, including hepatocellular carcinoma cells (Jiang et al, ), vascular smooth muscle cells (Pan et al, ), and bovine mammary epithelial cells (Li et al, ). In agreement, we found that mTOR signaling pathway was activated or inhibited in response to the low or high concentration of NaHS, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…As a gaseous signaling molecule, H 2 S exerts its physiological functions through different manners (Nikolic, Li, Liu, & Wang, ), including modifying proteins (Modis et al, ), affecting ion channels (Papapetropoulos et al, ), influencing metabolism (Sun et al, ), and regulating cell signaling such as Nrf 2 pathway (Calvert et al, ), NF‐κB pathway (De Cicco et al, ), PI3 K/Akt pathway (Chen et al, ) and mTOR pathway (Wang et al, ). It has been well documented that the PI3 K/Akt (De Cicco et al, ; Meng, Yuan, et al, ; Meng, Zhang, et al, ) and mTOR (Jiang et al, ; Li et al, ; Pan, Li, Huang, & Zhang, ) signaling pathway are involved in the regulation of the cell proliferation. However, the mechanism by which H 2 S modulates the PMECs proliferation are still not clear.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Exogenous H₂S exerts biphasic effects on porcine mammary epithelial cells proliferation through PI3K/Akt‐mTOR signaling pathway

Zhang

Yuan

et al. 2018

Journal Cellular Physiology

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This study aimed to investigate the effects of exogenous H S on the proliferation of porcine mammary gland epithelial cells (PMECs) and explore the underlying mechanisms. We found that exposure of PMECs to NaHS, at concentrations ranging from 10 to 200 µM, stimulated cell proliferation. However, high concentration of NaHS (600 µM) inhibited PMECs proliferation. Accordingly, 10 µM NaHS significantly increased the percentage of cells undergoing DNA replication, elevated the mRNA and/or protein expression of Cyclin A2, Cyclin D1/3, Cyclin E2 and PCNA, and decreased p21 mRNA expression. In contrast, 600 µM NaHS elicited the opposite effects to that of 10 µM NaHS. In addition, PI3 K/Akt and mTOR signaling pathways were activated or inhibited in response to 10 or 600 µM NaHS, respectively. Furthermore, the promotion of PMECs proliferation, the change of proliferative genes expression, and the activation of mTOR signaling pathway induced by 10 µM NaHS were effectively blocked by PI3 K inhibitor Wortmannin. Similarly, inhibition of mTOR with Rapamycin totally abolished the 10 µM NaHS-induced stimulation of PMECs proliferation and alteration of proliferative genes expression, with no influence on PI3 K/Akt signaling pathway. Moreover, constitutive activation of Akt pathway via transfection of Akt-CA completely eliminated the inhibition of PMECs proliferation and mTOR signaling pathway, and the change of proliferative genes expression induced by 600 µM NaHS. In conclusion, our findings provided evidence that exogenous H S supplied by NaHS exerted biphasic effects on PMECs proliferation, with stimulation at lower doses and suppression at high dose, through the intracellular PI3 K/Akt-mTOR signaling pathway.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Exogenous H₂S exerts biphasic effects on porcine mammary epithelial cells proliferation through PI3K/Akt‐mTOR signaling pathway

Zhang

Yuan

et al. 2018

Journal Cellular Physiology

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“…Therefore, in-depth investigation of the detailed roles of miRNAs and their underlying mechanisms in TSCC is likely to provide therapeutic targets for the treatment of patients with this aggressive disease. miRNA (miR)-758 is a miRNA that has been frequently studied in non-small cell lung cancer (20), hepatocellular carcinoma (21) and cervical cancer (22). However, to date, the expression patterns and roles of miR-758 in TSCC have remained largely unknown.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑758 inhibits tumorous behavior in tongue squamous cell carcinoma by directly targeting metadherin

Zhang

Zhao

2019

Mol Med Report

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Numerous microRNAs (miRNAs) are dysregulated in tongue squamous cell carcinoma (TSCC), and their dysregulation has been demonstrated to have a strong correlation with TSCC progression via regulation of their targets. Therefore, miRNAs have potential use in the diagnosis and treatment of patients with TSCC. In the present study, miRNA-758 (miR-758) expression in TSCC tissues and cell lines was detected through reverse transcription-quantitative polymerase chain reaction, and the effects of miR-758 on TSCC cell proliferation and invasion were investigated by using Cell Counting kit-8 and Transwell invasion assays. A luciferase reporter assay was performed to determine the target interaction between miR-758 and metadherin (MTDH) in TSCC cells. The results revealed that miR-758 was downregulated in TSCC tissues and cell lines. miR-758 overexpression restricted the proliferation and invasion of TSCC cells. Additionally, MTDH was verified as a direct target gene of miR-758 in TSCC cells. Furthermore, MTDH was observed to be upregulated in TSCC tissues, and the upregulation of MTDH was inversely correlated with miR-758 expression. Moreover, restored MTDH expression significantly counteracted the suppressive effects of miR-758 overexpression on TSCC cells. These results suggested that miR-758 may prevent TSCC progression and development by directly targeting MTDH, thereby providing evidence that miR-758 is a novel therapeutic target for the treatment of patients with TSCC.

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“…Numerous miRNAs are downregulated or upregulated in HCC, such as miR-21 (13), miR-493 (14), miR-873 (15) and miR-3662 (16). Upregulated miRNAs usually serve as oncogenes (17,18), whereas lowly expressed miRNAs display tumor-suppressor activity (19,20) in regards to HCC initiation and development. Therefore, inhibition or restoration of a specific miRNA might be an effective therapeutic technique for HCC treatment.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑466 inhibits the aggressive behaviors of hepatocellular carcinoma by directly targeting metadherin

et al. 2018

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Numerous microRNAs (miRNAs) have been demonstrated to be downregulated or upregulated in hepatocellular carcinoma (HCC) and play important roles in its occurrence and development. Therefore, the investigation of miRNAs and their functions implicated in the genesis and development of HCC may provide key clues for the identification of effective therapeutic approaches for patients with this disease. The aims of the present study were to detect miRNA-466 (miR-466) expression in HCC tissues and cell lines and to determine its effects on HCC cell proliferation, apoptosis and metastasis, as well as to explore the mechanisms underlying the tumor-suppressing roles of miR-466 in HCC. In the present study, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to detect miR-466 expression in HCC tissues and cell lines. The effects of miR-466 upregulation on HCC cell proliferation, apoptosis, migration and invasion were determined using Cell Counting Kit-8 assay, flow cytometry analysis and Transwell chamber assay, respectively. The potential target gene of miR-466 was predicted using bioinformatic analysis, which was further confirmed by luciferase reporter assay, RT-qPCR and western blot analysis. It was found that miR-466 was obviously decreased in HCC tissues and cell lines. The results of functional experiments revealed that restoration of miR-466 expression suppressed the proliferation, induced apoptosis, and reduced the metastasis of HCC cells. In addition, metadherin (MTDH) was identified as a direct target of miR-466 in HCC cells. Furthermore, MTDH was upregulated in HCC tissues, which was inversely correlated with the miR-466 level. Moreover, inhibition of MTDH displayed similar tumor-suppressing roles as miR-466 upregulation in HCC cells. In addition, MTDH reintroduction restored the tumor-suppressor activity of miR-466 overexpression in HCC cells. These findings suggest that miR-466 is a potential therapeutic tool for HCC therapy.

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MiR-758-3p suppresses proliferation, migration and invasion of hepatocellular carcinoma cells via targeting MDM2 and mTOR

Cited by 47 publications

References 32 publications

Exogenous H₂S exerts biphasic effects on porcine mammary epithelial cells proliferation through PI3K/Akt‐mTOR signaling pathway

Exogenous H₂S exerts biphasic effects on porcine mammary epithelial cells proliferation through PI3K/Akt‐mTOR signaling pathway

MicroRNA‑758 inhibits tumorous behavior in tongue squamous cell carcinoma by directly targeting metadherin

MicroRNA‑466 inhibits the aggressive behaviors of hepatocellular carcinoma by directly targeting metadherin

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MiR-758-3p suppresses proliferation, migration and invasion of hepatocellular carcinoma cells via targeting MDM2 and mTOR

Cited by 47 publications

References 32 publications

Exogenous H2S exerts biphasic effects on porcine mammary epithelial cells proliferation through PI3K/Akt‐mTOR signaling pathway

Exogenous H2S exerts biphasic effects on porcine mammary epithelial cells proliferation through PI3K/Akt‐mTOR signaling pathway

MicroRNA‑758 inhibits tumorous behavior in tongue squamous cell carcinoma by directly targeting metadherin

MicroRNA‑466 inhibits the aggressive behaviors of hepatocellular carcinoma by directly targeting metadherin

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Exogenous H₂S exerts biphasic effects on porcine mammary epithelial cells proliferation through PI3K/Akt‐mTOR signaling pathway

Exogenous H₂S exerts biphasic effects on porcine mammary epithelial cells proliferation through PI3K/Akt‐mTOR signaling pathway