The plant sesquiterpene lactone parthenolide inhibits Wnt/β-catenin signaling by blocking synthesis of the transcriptional regulators TCF4/LEF1

Zhu, Xin; Yuan, Chunmao; Tian, Chenyang; Li, Chen; Nie, Fan; Song, Xiaomin; Zeng, Rong; Wu, Dianqing; Hao, Xiao‐Jiang; Li, Lin

doi:10.1074/jbc.m117.819300

Cited by 35 publications

(32 citation statements)

References 39 publications

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“…WNT2B interacts with frizzled receptor and activates the Wnt signaling pathway, which leads to the increased expression of β-catenin in the cytoplasm (23). Subsequently, the β-catenin protein translocates from the cytoplasm into the nucleus and promotes the transcriptional effect of TcF4 (28,29). Previous studies have reported that WNT2B acts as an oncogene in a number of tumors and is positively associated with tumor progression.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑137 suppresses the proliferation, migration and invasion of cholangiocarcinoma cells by targeting WNT2B

et al. 2020

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It is widely known that abnormal regulation of microRNAs (miRNAs/miRs) may contribute to the occurrence or development of tumors. The objective of the present study was to elucidate the function and underlying mechanism of miR-137 in the progression of cholangiocarcinoma (ccA). The expression levels of miR-137 in ccA tissues and cell lines were measured using reverse transcription-quantitative PcR. The role of miR-137 in the proliferation of ccA cells was assessed using the cell counting Kit-8 assay, colony formation assay and cell cycle distribution analysis, while its effects on the migration and invasion of ccA cells were evaluated using Transwell assays. The function of miR-137 on ccA growth in vivo was also investigated using a xenograft mouse model. Furthermore, the association between miR-137 and Wnt family member 2B (WNT2B) was analyzed using bioinformatics, double luciferase assay and western blotting. It was verified that the expression of miR-137 was low in ccA tissues and cell lines, whereas increased expression of miR-137 significantly suppressed cell proliferation, decreased colony formation ability and induced G1 phase arrest. miR-137 overexpression suppressed the migration and invasion ability of TFK-1 and HuccT1 cells. Furthermore, the results of the xenograft mouse model assays revealed that miR-137 overexpression decreased tumor growth in vivo. The results of bioinformatics analysis and dual luciferase reporter assays demonstrated that WNT2B is directly regulated by miR-137. The expression of WNT2B and Wnt-pathway-related proteins was decreased when miR-137 was overexpressed. Restoring the expression of WNT2B notably reversed the inhibitory effect of miR-137 on CCA cells. Therefore, the findings of the present study demonstrated that miR-137 acts as a suppressor in ccA and inhibits ccA cell proliferation, migration and invasion through suppressing the expression of WNT2B.

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Section: Discussionmentioning

confidence: 99%

MicroRNA‑137 suppresses the proliferation, migration and invasion of cholangiocarcinoma cells by targeting WNT2B

et al. 2020

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“…With the rapid progress in transcriptome sequencing, different lncRNAs are being identified to be related to different diseases, including RA. 23,24 Previous study indicated the potential role of MEG3 in RA. 25 Also, it is important to understand the effect of MEG3 in RA as well as the underlying molecular mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…With the rapid progress in transcriptome sequencing, different lncRNAs are being identified to be related to different diseases, including RA . Previous study indicated the potential role of MEG3 in RA .…”

Section: Discussionmentioning

confidence: 99%

LncRNA MEG3 inhibits rheumatoid arthritis through miR‐141 and inactivation of AKT/mTOR signalling pathway

Liu

Meng

et al. 2019

J Cellular Molecular Medi

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Rheumatoid arthritis (RA) is a chronic inflammation mediated by autoimmune responses. MEG3, a kind of long noncoding RNA (lncRNA), participates in cell proliferation in cancer tissues. However, the correlation between MEG3 and RA is yet unclear. Therefore, to clarify how MEG3 works in RA, we performed a series of experiments using RA samples. We found that MEG3 was downregulated in the fibroblast‐like synoviocytes of RA patients (RA‐FLS), in comparison with healthy subjects. MEG3 was also down‐regulated evidently in lipopolysaccharide (LPS)‐treated chondrocyte. As part of our experiments, MEG3 was overexpressed in chondrocyte by transfection with lentivirus containing sequences encoding MEG3. In addition, in presence of LPS, reductions were identified not only in the cell proliferation, but also in the generation of interleukin‐23 (IL‐23), which, however were reversed in the lentivirus (containing MEG3‐encoding sequences)‐transfected chondrocytes. Up‐regulated MEG3 resulted in an increase the level of Ki67. Moreover, MEG3 was negatively correlated with miR‐141, and miR‐141 was up‐regulated in LPS‐treated chondrocyte. Inhibitory effects of MEG3 overexpression, mentioned above, were partially abolished by overexpressed miR‐141. Further, animal experiment also showed the inhibitory effect of MEG3 in overexpression on the AKT/mTOR signaling pathway. In‐vivoexperiments also showed that cell proliferation was facilitated by MEG3 overexpression with inhibited inflammation. In summary, the protective role of MEG3 in RA was proved to be exerted by the increase in the rate of proliferation, which might correlate to the regulatory role of miR‐141 and AKT/mTOR signal pathway, suggesting that MEG3 holds great promise as a therapeutic strategy for RA.

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“…RPL10 is a component of the 60S ribosome. The use of parthenolide probe showed that deprivation of RPL10 decreased the levels of TCF4/LEF1 but had no effects on β-catenin levels, indicating a selectivity of the 60S ribosome in regulating protein synthesis (Zhu et al, 2018).…”

Section: Plant Natural Product Modulators Of Wnt Signalingmentioning

confidence: 99%

Natural product sciences: an integrative approach to the innovations of plant natural products

Shen

Hao

2020

Sci. China Life Sci.

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The study on plant natural products not only helps us understand that their structural diversity is the inevitable result of plant species diversity, but also helps us understand certain rules and unity of the inevitable connection between the two. The diversity and complexity of chemical structures of many natural products are beyond imagination before we elucidated their structures. The question that follows is what is the biological significance of these natural products. Intrigued by the relationship between plant resources, natural products and biological functions, the Hao laboratory has taken an integrative approach that employs tools and knowledge from multi-disciplines, including natural product chemistry, chemical ecology and chemical biology, to unveil the effects of plant natural products on plant resistance to diseases, and environmental acclimations. Collaborating with cell biologists, the research has resulted in discovery of new mechanisms of cellular signaling and lead compounds.

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The plant sesquiterpene lactone parthenolide inhibits Wnt/β-catenin signaling by blocking synthesis of the transcriptional regulators TCF4/LEF1

Cited by 35 publications

References 39 publications

MicroRNA‑137 suppresses the proliferation, migration and invasion of cholangiocarcinoma cells by targeting WNT2B

MicroRNA‑137 suppresses the proliferation, migration and invasion of cholangiocarcinoma cells by targeting WNT2B

LncRNA MEG3 inhibits rheumatoid arthritis through miR‐141 and inactivation of AKT/mTOR signalling pathway

Natural product sciences: an integrative approach to the innovations of plant natural products

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