MiR-1 suppresses tumor cell proliferation in colorectal cancer by inhibition of Smad3-mediated tumor glycolysis

Xu, Wei; Zhang, Zijing; Zou, Kejian; Cheng, Yang; Yang, Min; Chen, Huan; Wang, Hongli; Zhao, Jin; Chen, Peiyu; He, Lin; Chen, Xinwen; Geng, Lanlan; Gong, Sitang

doi:10.1038/cddis.2017.60

Cited by 98 publications

(79 citation statements)

References 49 publications

(49 reference statements)

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“…Cell proliferation was measured using a cell counting kit-8 (CCK-8) (Dojindo) as described by Xu et al [18]. In brief, the cells were seeded into 96-well plate at a concentration of 5 × 10 3 cells per well.…”

Section: Cell Proliferation Assaymentioning

confidence: 99%

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CD147 Expression Is Associated with Tumor Proliferation in Bladder Cancer via GSDMD

Peng

Jiang

Guo

et al. 2020

BioMed Research International

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Purpose. CD147, also known as BSG, is a type I transmembrane glycoprotein that belonged to immunoglobulin superfamily. Mature CD147 is an N-linked glycosylated protein and exists on the transmembrane and as soluble forms in tumors. However, the function of CD147 in cell proliferation of bladder cancer (BC) remains to be elucidated. Methods. e study included 159 patients with BC and 68 healthy controls. e expression of CD147 and gasdermin D (GSDMD) was analyzed by immunohistochemistry (IHC). Western blotting was performed to detect the expression of proteins in BC cells. e relationship between CD147 and GSDMD was analyzed by the IHC score. Results. e expression of CD147 was significantly increased in BC when compared to healthy controls, and the level of CD147 was correlated with tumor proliferation characterized by Ki-67, which is a cell proliferation antigen. In addition, CD147 treatment of BC cells increased the expression of GSDMD, leading to increased Ki-67 expression, while CD147 blockade with peptide in BC significantly reduced GSDMD expression, resulting in reduced cell proliferation. Furthermore, overexpression of GSDMD markedly overcame the inhibitory effect of CD147 peptide on tumor proliferation. BC patients with overexpression of CD147 showed correlation with GSDMD and demonstrated significantly poorer prognosis and overall survival rate. Conclusion. ese findings suggested that high expression of CD147 contributed to tumor proliferation in BC via GSDMD, which might in turn act as an unfavorable prognostic marker.

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Section: Cell Proliferation Assaymentioning

confidence: 99%

“…Western blot analysis was performed as described previously [18]. In brief, the total proteins were collected and subjected to SDS-PAGE and then transferred onto a PDVF membrane.…”

Section: Western Blot Analysismentioning

confidence: 99%

CD147 Expression Is Associated with Tumor Proliferation in Bladder Cancer via GSDMD

Peng

Jiang

Guo

et al. 2020

BioMed Research International

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“…Immunohistochemistry and immunofluorescence were performed as described in our previous work. 26,27 The sections were deparaffinized, rehydrated, blocked with goat serum and incubated with…”

Section: Immunohistochemistry (Ihc) and Immunofluorescence(if)mentioning

confidence: 99%

Inhibition of CREB‐mediated ZO‐1 and activation of NF‐κB‐induced IL‐6 by colonic epithelial MCT4 destroys intestinal barrier function

Zhang

Wang

et al. 2019

Cell Proliferation

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Objective Inflammatory bowel disease (IBD) is a disorder intestinal inflammation and impaired barrier function, associated with increased epithelial expression of monocarboxylate transporter 4 (MCT4). However, the specific non‐metabolic function and clinical relevance of MCT4 in IBD remain to be fully elucidated. Methods Lentivirus‐mediated overexpression of MCT4 was used to assess the role of MCT4 in transcriptionally regulating ZO‐1 and IL‐6 expression by luciferase assays, WB and ChIP. IP was used to analyse the effect of MCT4 on the interaction NF‐κB‐CBP or CREB‐CBP, and these MCT4‐mediated effects were confirmed in vivo assay. Results We showed that ectopic expression of MCT4 inhibited ZO‐1 expression, while increased pro‐inflammatory factors expression, leading to destroy intestinal epithelial barrier function in vitro and in vivo. Mechanistically, MCT4 contributed NF‐κB p65 nuclear translocation and increased the binding of NF‐κB p65 to the promoter of IL‐6, which is attributed to MCT4 enhanced NF‐κB‐CBP interaction and dissolved CREB‐CBP complex, resulting in reduction of CREB activity and CREB‐mediated ZO‐1 expression. In addition, treatment of experimental colitis with MCT4 inhibitor α‐cyano‐4‐hydroxycinnamate (CHC) ameliorated mucosal intestinal barrier function, which was due to attenuation of pro‐inflammation factors expression and enhancement of ZO‐1 expression. Conclusion These findings suggested a novel role of MCT4 in controlling development of IBD and provided evidence for potential targets of IBD.

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“…miRs are a class of small (19-25 nucleotides) non-coding RNAs, binding messenger RNAs at their 3’-untranslated regions (3’-UTRs) to suppress their targets expression either by inhibiting protein translation or causing mRNA cleavage [13]. Increasing anti- or pro-Warburg effect miRs have been identified [14-17]. However, the miR-regulatory network mediating the anti-Warburg effect of 20(S)-Rg3 has yet to be revealed.…”

Section: Introductionmentioning

confidence: 99%

Ginsenoside 20(S)-Rg3 Inhibits the Warburg Effect Via Modulating DNMT3A/ MiR-532-3p/HK2 Pathway in Ovarian Cancer Cells

Zhou

Zheng

et al. 2018

Cell Physiol Biochem

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Background/Aims: The Warburg effect is one of the main energy metabolism features supporting cancer cell growth. 20(S)-Rg3 exerts anti-tumor effect on ovarian cancer partly by inhibiting the Warburg effect. microRNAs are important regulators of the Warburg effect. However, the microRNA regulatory network mediating the anti-Warburg effect of 20(S)-Rg3 was largely unknown. Methods: microRNA deep sequencing was performed to identify the 20(S)-Rg3-influenced microRNAs in SKOV3 ovarian cancer cells. miR-532-3p was overexpressed by mimic532-3p transfection in SKOV3 and A2780 cells or inhibited by inhibitor532-3p transfection in 20(S)-Rg3-treated cells to examine the changes in HK2 and PKM2 expression, glucose consumption, lactate production and cell growth. Dual-luciferase reporter assay was conducted to verify the direct binding of miR-532-3p to HK2. The methylation status in the promoter region of pre-miR-532-3p gene was examined by methylation-specific PCR. Expression changes of key molecules controlling DNA methylation including DNMT1, DNMT3A, DNMT3B, and TET1-3 were examined in 20(S)-Rg3-treated cells. DNMT3A was overexpressed in 20(S)-Rg3-treated cells to examine its influence on miR-532-3p level, HK2 and PKM2 expression, glucose consumption and lactate production. Results: Deep sequencing results showed that 11 microRNAs were increased and 9 microRNAs were decreased by 20(S)-Rg3 in SKOV3 cells, which were verified by qPCR. More than 2-fold increase of miR-532-3p was found in 20(S)-Rg3-treated SKOV3 cells. Forced expression of miR-532-3p reduced HK2 and PKM2 expression, glucose consumption and lactate production in SKOV3 and A2780 ovarian cancer cells. Inhibition of miR-532-3p antagonized the suppressive effect of 20(S)-Rg3 on HK2 and PKM2 expression, glucose consumption and lactate production in ovarian cancer cells. Dual-luciferase reporter assay showed that miR-532-3p directly suppressed HK2 rather than PKM2. miR-532-3p level was controlled by the methylation in the promoter region of its host gene. 20(S)-Rg3 inhibited DNMT3A expression while exerted insignificant effect on DNMT1, DNMT3B and TET1-3. 20(S)-Rg3 reversed DNMT3A-mediated methylation in the promoter of the host gene of miR-532-3p, and thus elevated miR-532-3p level followed by suppression of HK2 and PKM2 expression, glucose consumption and lactate production. Conclusions: 20(S)-Rg3 modulated microRNAs to exert the anti-tumor effect in ovarian cancer. 20(S)-Rg3 lessened the DNMT3A-mediated methylation and promoted the suppression of miR-532-3p on HK2 to antagonize the Warburg effect of ovarian cancer cells.

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MiR-1 suppresses tumor cell proliferation in colorectal cancer by inhibition of Smad3-mediated tumor glycolysis

Cited by 98 publications

References 49 publications

CD147 Expression Is Associated with Tumor Proliferation in Bladder Cancer via GSDMD

CD147 Expression Is Associated with Tumor Proliferation in Bladder Cancer via GSDMD

Inhibition of CREB‐mediated ZO‐1 and activation of NF‐κB‐induced IL‐6 by colonic epithelial MCT4 destroys intestinal barrier function

Ginsenoside 20(S)-Rg3 Inhibits the Warburg Effect Via Modulating DNMT3A/ MiR-532-3p/HK2 Pathway in Ovarian Cancer Cells

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