PPARγ inhibits ovarian cancer cells proliferation through upregulation of miR-125b

Luo, Siyang; Wang, Jidong; Ma, Ying; Yao, Zhenwei; Pan, Hongjuan

doi:10.1016/j.bbrc.2015.04.023

Cited by 37 publications

(21 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is known that PPARγ can promote the expression of miR-125b by directly binding to the responsive element in miR-125b gene promoter region [26]. In our study, we explored whether PPARγ participated in the regulation of miR-125b.…”

Section: Resultsmentioning

confidence: 99%

FAK regulates E-cadherin expression via p-SrcY416/p-ERK1/2/p-Stat3Y705 and PPARγ/miR-125b/Stat3 signaling pathway in B16F10 melanoma cells

et al. 2017

View full text Add to dashboard Cite

Focal adhesion kinase (FAK) is involved in tumor cell migration and metastasis. However, the underlying mechanism remains unclear. Here, we present a signaling pathway involved in the regulation of melanoma cell migration by FAK. We found that the interference of FAK expression suppressed B16F10 cell migration/metastasis, and altered the expressions of genes involved in melanoma migration/metastasis. The down-regulation of FAK inhibited the expression of p-SrcY416, p-ERK1/2, Stat3 and p-Stat3Y705, while promoted the expression of PPARγ, miR-125b and E-cadherin. Then we found that FAK inhibited E-cadherin expression via p-SrcY416/p-ERK1/2/ p-Stat3Y705 and PPARγ/miR-125b/Stat3 signaling pathway in B16F10 cell. Moreover, miR-125b inhibited B16F10 cell migration. Furthermore, we repeated the key data with human melanoma cell line A375. The results obtained from A375 cells fell in line with those from B16F10 cells. Using Oncomine database, we found that the mRNA levels of FAK, Src, ERK1/2 and Stat3 increased, while the mRNA levels of PPARγ, C21orf34 (miR-125b host gene) and E-cadherin decreased in human metastatic melanoma. The data from human breast cancer confirmed those from metastatic melanoma.Taken together, our study suggests that down-regulation of FAK promotes E-cadherin expression via p-SrcY416/p-ERK1/2/p-Stat3Y705 and PPARγ/miR-125b/Stat3 signaling pathway. Our findings provide a novel explanation regarding how FAK promotes melanoma cell migration, suggesting that FAK might be a potential target for melanoma therapy.

show abstract

Section: Resultsmentioning

confidence: 99%

FAK regulates E-cadherin expression via p-SrcY416/p-ERK1/2/p-Stat3Y705 and PPARγ/miR-125b/Stat3 signaling pathway in B16F10 melanoma cells

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Therefore, the under‐expression of miR‐627‐5p might lead to the aberrant overexpression of BCL3 in HCC. Previous investigations have recognized miR‐19b and miR‐125b as post‐transcriptional regulators of BCL3 in gastric cancer and ovarian cancer, respectively. BCL3 mediates HBx‐induced upregulation of Cyclin D1 in HBV‐related HCC .…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐627‐5p inhibits the proliferation of hepatocellular carcinoma cells by targeting BCL3 transcription coactivator

Wang

Chen

Wang

et al. 2019

Clin Exp Pharma Physio

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is a common malignant tumour. An increasing number of studies indicate that microRNAs (miRNAs) are critical regulators in the carcinogenesis and progression of HCC. MiR-627-5p has been identified as a tumour suppressor in colorectal cancer and glioblastoma multiforme. However, the function of miR-627-5p in HCC progression remains unclear yet. In our present study, miR-627-5p was determined to be low-expressed in HCC tissues and cell lines. Furthermore, miR-627-5p was expressed at significantly lower levels in HCC tissues with tumour size >5 cm or advanced tumour stages (III+IV). Additionally, HCC patients with low miR-627-5p level had a significantly poorer overall survival. Functionally, ectopic expression of miR-627-5p obviously inhibited the proliferation, and induced G1 phase arrest and apoptosis of Hep3B and SMMC-7721 cells. Conversely, miR-627-5p silencing facilitated HCC cell proliferation, cell cycle progression and apoptosis resistance. In vivo experiments further confirmed that miR-627-5p overexpression repressed the growth of Hep3B cells in mice. Mechanistically, BCL3 transcription coactivator was predicted as a direct target of miR-627-5p. MiR-627-5p overexpression reduced, whereas miR-627-5p knockdown enhanced the expression of BCL3 protein in HCC cells. Luciferase reporter assay confirmed the direct binding between miR-627-5p and 3′UTR of BCL3.The expression of BCL3 protein was negatively correlated with miR-627-5p level in HCC tissues. More importantly, re-expression of BCL3 partially reversed miR-627-5p induced inhibitory effects on Hep3B cells. In conclusion, these results demonstrated that miR-627-5p functioned as a tumour suppressor in HCC possibly by attenuating BCL3. This finding might offer a new therapeutic target for HCC treatment. K E Y W O R D SBCL3, hepatocellular carcinoma, miR-627-5p, proliferation, tumour growth

show abstract

“…Consistent with its oncogenic function, Bcl3 can transform cells and induce their proliferation and tumor growth (24). Recent studies have shown that miR-125b, which targets Bcl3, is down-regulated in ovarian cancer (OC) 2 tissues (25,26), suggesting an increased Bcl3 expres-sion in ovarian cancer. However, the Bcl3 expression in OC has not been investigated, and its function in OC cells remains unknown.…”

mentioning

confidence: 99%

The proto-oncogene Bcl3 induces immune checkpoint PD-L1 expression, mediating proliferation of ovarian cancer cells

Zou

Uddin

Padmanabhan

et al. 2018

Journal of Biological Chemistry

View full text Add to dashboard Cite

The proto-oncogene Bcl3 induces survival and proliferation in cancer cells; however, its function and regulation in ovarian cancer (OC) remain unknown. Here, we show that expression is increased in human OC tissues. Surprisingly, however, we found that in addition to promoting survival, proliferation, and migration of OC cells, Bcl3 promotes both constitutive and interferon-γ (IFN)-induced expression of the immune checkpoint molecule PD-L1. The Bcl3 expression in OC cells is further increased by IFN, resulting in increased transcription. The mechanism consists of an IFN-induced, Bcl3- and p300-dependent promoter occupancy by Lys-314/315 acetylated p65 NF-κB. Blocking PD-L1 by neutralizing antibody reduces proliferation of OC cells overexpressing Bcl3, suggesting that the pro-proliferative effect of Bcl3 in OC cells is partly mediated by PD-L1. Together, this work identifies PD-L1 as a novel target of Bcl3, and links Bcl3 to IFNγ signaling and PD-L1-mediated immune escape.

show abstract

PPARγ inhibits ovarian cancer cells proliferation through upregulation of miR-125b

Cited by 37 publications

References 35 publications

FAK regulates E-cadherin expression via p-SrcY416/p-ERK1/2/p-Stat3Y705 and PPARγ/miR-125b/Stat3 signaling pathway in B16F10 melanoma cells

FAK regulates E-cadherin expression via p-SrcY416/p-ERK1/2/p-Stat3Y705 and PPARγ/miR-125b/Stat3 signaling pathway in B16F10 melanoma cells

MicroRNA‐627‐5p inhibits the proliferation of hepatocellular carcinoma cells by targeting BCL3 transcription coactivator

The proto-oncogene Bcl3 induces immune checkpoint PD-L1 expression, mediating proliferation of ovarian cancer cells

Contact Info

Product

Resources

About