miR-598 inhibits metastasis in colorectal cancer by suppressing JAG1/Notch2 pathway stimulating EMT

Chen, Jia; Zhang, Haichen; Chen, Ying; Qiao, Guanglei; Jiang, Weihua; Ni, Peihong; Liu, Xiangfan; Ma, Lijun

doi:10.1016/j.yexcr.2017.01.022

Cited by 71 publications

(64 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We found that Notch2 3′‐UTR includes one potential miR‐181c target site conserved in humans and mice. Current evidence has demonstrated that Notch2 regulates the expression of several mesenchymal genes at the transcriptional level . We postulated that the effect of miR‐181c on the EMT process may be mediated by Notch2.…”

Section: Resultsmentioning

confidence: 92%

miR‐181c protects CsA‐induced renal damage and fibrosis through inhibiting EMT

Sun

Min

et al. 2017

FEBS Letters

View full text Add to dashboard Cite

Cyclosporine A (CsA), a widely used immunosuppressive drug in organ transplantation and autoimmune disorders, frequently induces renal damage and fibrosis. Recent evidence has implicated epithelial-mesenchymal transition (EMT) in CsA-induced nephrotoxicity. Microarray analysis disclosed miR-181c as the microRNA most dramatically repressed by CsA. Downregulation of miR-181c expression at the transcriptional level by CsA is dependent on the transcription factor Nrf2. miR-181c mimics or inhibitors attenuate or aggravate CsA-induced EMT gene changes, respectively. Importantly, in Nrf2-/- mice, CsA-induced renal damage, fibrosis, and EMT gene changes are restored by miR-181c mimics. Mechanistically, we identified Notch2 as a potential target of miR-181c. Collectively, our data support the notion that miR-181c may serve as an important factor for protecting renal tissues from CsA-induced nephrotoxicity.

show abstract

Section: Resultsmentioning

confidence: 92%

miR‐181c protects CsA‐induced renal damage and fibrosis through inhibiting EMT

Sun

Min

et al. 2017

FEBS Letters

View full text Add to dashboard Cite

show abstract

“…The overexpression of miR-598 suppressed the proliferation, migration, and invasion of osteosarcoma cells [13]. Moreover, miR-598 always inhibits EMT and suppresses metastasis in colorectal cancer by targeting JAG1 [14]. However, the role of miR-598 in NSCLC has not been reported previously.…”

Section: Discussionmentioning

confidence: 99%

“…Another study by Chen et al . revealed that the over-expression of miR-598 suppresses the metastasis in colorectal cancer by targeting JAG1 [14]. Nonetheless, the role of miR-598 in NSCLC has not yet been reported.…”

Section: Introductionmentioning

confidence: 99%

MiR-598 Suppresses Invasion and Migration by Negative Regulation of Derlin-1 and Epithelial-Mesenchymal Transition in Non-Small Cell Lung Cancer

Yang

Wei

Qin

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: MicroRNAs regulate a wide range of biological processes of non-small cell lung cancer (NSCLC). Although miR-598 has been reported to act as a suppressor in osteosarcoma and colorectal cancer, the physiological function of miR-598 in NSCLC remains unknown. In this study, the role of miR-598 in NSCLC was investigated. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to estimate the expression of miR-598 and Derlin-1 (DERL1) in both NSCLC tissues and cell lines. Immunohistochemistry (IHC) analyzed the association between the miR-598 expression and epithelial-mesenchymal transition (EMT) hallmark genes (E-cadherin, Vimentin) by staining the tumors representative of the high- and low-expression groups. The effect of miR-598 and DERL1 on invasion and migration was determined in vitro using transwell and wound-healing assays. The molecular mechanism underlying the relevance between miR-598 and DERL1 was elucidated by luciferase assay and Western blot. Western blot assessed the expression levels of EMT hallmark genes in cell lines. Xenograft tumor formation assay was conducted as an in vivo experiment. Results: In this study, a relatively low level of miR-598 and high DERL1 expressions were found in NSCLC specimens and cell lines. IHC results established a positive correlation between the miR-598 expression and E-cadherin and a negative with Vimentin. DERL1 was verified as a direct target of miR-598 by luciferase assay. In vitro, the over-expression of miR-598 negatively regulated DERL1 and EMT for the suppression of invasion and migration. In vivo, the over-expression of miR-598 could inhibit tumor cell metastasis in NSCLC. Conclusions: These findings for the first time revealed that miR-598, as a tumor suppressor, negatively regulate DERL1 and EMT to suppress the invasion and migration in NSCLC, thereby putatively serving as a novel therapeutic target for NSCLC clinical treatment.

show abstract

“…A variety of signaling pathways are involved in tumor migration and invasion (24)(25)(26). LKB1/AMPK signaling has gained great attention in recent years.…”

Section: Discussionmentioning

confidence: 99%

Thymoquinone inhibits metastatic phenotype and epithelial‑mesenchymal transition in renal cell carcinoma by regulating the LKB1/AMPK signaling pathway

Kou

et al. 2018

Oncol Rep

View full text Add to dashboard Cite

Thymoquinone, isolated from the seeds of Nigella sativa, has exhibited antitumor properties in a variety of cancer types. However, few studies have investigated the effect of thymoquinone (TQ) on migration and invasion in renal cell carcinoma (RCC). In the present study, our results confirmed that TQ significantly inhibited the migration and invasion of the human RCC 769‑P and 786‑O cell lines, as demonstrated by wound healing and Transwell assays. Additionally, TQ upregulated the expression of E‑cadherin and downregulated the expression of Snail, ZEB1 and vimentin at the mRNA and protein levels in a concentration‑dependent manner. Subsequently, the phosphorylation levels of liver kinase B1 (LKB1) and AMP‑activated protein kinase (AMPK) were increased upon TQ treatment. To further validate the role of LKB1/AMPK signaling, we revealed that TQ‑mediated increase of E‑cadherin level and reduction of Snail level could be further enhanced by LKB1 overexpression. Furthermore, co‑treatment with the AMPK inhibitor Compound C attenuated the anti‑metastatic effect of TQ on RCC and partially abrogated the high expression of E‑cadherin and the low expression of Snail mediated by TQ. In contrast, the AMPK activator AICAR demonstrated the opposite effect. Collectively, the present study revealed that TQ could markedly suppress the metastatic phenotype and reverse the epithelial‑mesenchymal transition in RCC by regulating the LKB1/AMPK signaling pathway, indicating that TQ may be a potential therapeutic candidate against RCC.

show abstract

miR-598 inhibits metastasis in colorectal cancer by suppressing JAG1/Notch2 pathway stimulating EMT

Cited by 71 publications

References 25 publications

miR‐181c protects CsA‐induced renal damage and fibrosis through inhibiting EMT

miR‐181c protects CsA‐induced renal damage and fibrosis through inhibiting EMT

MiR-598 Suppresses Invasion and Migration by Negative Regulation of Derlin-1 and Epithelial-Mesenchymal Transition in Non-Small Cell Lung Cancer

Thymoquinone inhibits metastatic phenotype and epithelial‑mesenchymal transition in renal cell carcinoma by regulating the LKB1/AMPK signaling pathway

Contact Info

Product

Resources

About