Hsa-miR-4271 downregulates the expression of constitutive androstane receptor and enhances in vivo the sensitivity of non-small cell lung cancer to gefitinib

Wang, Chunzhan; Ding, Shengguang; Sun, Baisheng; Shen, Liang; Xiao, Ling; Han, Zhihai; Huang, Haitao

doi:10.1016/j.phrs.2020.105110

Cited by 29 publications

(23 citation statements)

References 59 publications

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“…Recently, results of a clinical trial (the COSMIC-021 trial) mentioned that Cabozantinib (an anti-angiogenesis drug that also targets MET) could be benefit for treatment (44). Therefore, it is valuable to focus on the significance of c-MET and the small molecular inhibitor of c-MET in the PC treatment (45,46). Another report revealed that the HGF/ETS pathway could be active in the TCGA molecular subgroup of TMPRSS2/ERG fused prostate cancers (50%) (47).…”

Section: Discussionmentioning

confidence: 99%

TPX2 Enhanced the Activation of the HGF/ETS-1 Pathway and Increased the Invasion of Endocrine-Independent Prostate Carcinoma Cells

et al. 2021

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The prognosis for endocrine-independent prostate carcinoma is still poor due to its highly metastatic feature. In the present work, TPX2 (the targeting protein for Xklp2), which is known as a micro-tubulin interacted protein, was identified as a novel coactivator of ETS-1, a transcription factor that plays a central role in mediating the metastasis of human malignancies. TPX2 enhanced the transcription factor activation of ETS-1 and increased the expression of ETS-1’s downstream metastasis-related genes, such as mmp3 or mmp9, induced by HGF (hepatocyte growth factor), a typical agonist of the HGF/c-MET/ETS-1 pathway. The protein-interaction between TPX2 and ETS-1 was examined using immunoprecipitation (IP). TPX2 enhanced the accumulation of ETS-1 in the nuclear and the recruitment of its binding element (EST binding site, EBS) located in the promoter region of its downstream gene, mmp9. Moreover, TPX2 enhanced the in vitro or in vivo invasion of a typical endocrine-independent prostate carcinoma cell line, PC-3. Therefore, TPX2 enhanced the activation of the HGF/ETS-1 pathway to enhance the invasion of endocrine-independent prostate carcinoma cells and thus it would be a promising target for prostate carcinoma treatment.

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Section: Discussionmentioning

confidence: 99%

TPX2 Enhanced the Activation of the HGF/ETS-1 Pathway and Increased the Invasion of Endocrine-Independent Prostate Carcinoma Cells

et al. 2021

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“…The Notch pathway-related factors in TNBC tissues, including the clinical specimens and the subcutaneous tumors, or TNBC cells were quantitatively examined using previously established qPCR methods ( 10 , 37 ). Ribonucleic acid was extracted from the TNBC cells or clinical tissues and reverse transcribed into cDNA.…”

Section: Methodsmentioning

confidence: 99%

“…The overall prognosis has been significantly improved by the widespread application of effective antitumor drug therapy, but the heterogeneous overall prognosis of triple-negative breast cancer (TNBC) remains unsatisfactory (6,7). Recently, the PARP inhibitor olaparib was approved for the treatment of TNBC with BRCA mutations (8)(9)(10). Although olaparib is considered to have a beneficial effect on patients with TNBC and prolong the survival of patients, there are differences in the sensitivity of individual patients to olaparib, and there are also reports of olaparib resistance (11,12).…”

Section: Introductionmentioning

confidence: 99%

miR-27-3p Enhances the Sensitivity of Triple-Negative Breast Cancer Cells to the Antitumor Agent Olaparib by Targeting PSEN-1, the Catalytic Subunit of Γ-Secretase

et al. 2021

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Olaparib has been used in the treatment of triple-negative breast cancer (TNBC) with BRCA mutations. In the present study, we demonstrated the effect of miR-27-3p on the γ-secretase pathway by regulating the sensitivity of TNBC cells to olaparib. miR-27-3p, a microRNA with the potential to target PSEN-1, the catalytic subunit of γ-secretase mediating the second step of the cleavage of the Notch protein, was identified by the online tool miRDB and found to inhibit the expression of PSEN-1 by directly targeting the 3’-untranslated region (3’-UTR) of PSEN-1. The overexpression of miR-27-3p inhibited the activation of the Notch pathway via the inhibition of the cleavage of the Notch protein, mediated by γ-secretase, and, in turn, enhanced the sensitivity of TNBC cells to the antitumor agent olaparib. Transfection with PSEN-1 containing mutated targeting sites for miR-27-3p or the expression vector of the Notch protein intracellular domain (NICD) almost completely blocked the effect of miR-27-3p on the Notch pathway or the sensitivity of TNBC cells to olaparib, respectively. Therefore, our results suggest that the miR-27-3p/γ-secretase axis participates in the regulation of TNBC and that the overexpression of miR-27-3p represents a potential approach to enhancing the sensitivity of TNBC to olaparib.

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“…For cell-based experiments, the molecular targeting agents were dissolved in DMSO (dimethyl sulfoxide) and diluted with phenol red-free DMEM (Thermo Fisher Scientific Corporation) ( 15 , 16 ). For the animal experiments, the formulation (oral liquid for the oral administration) of molecular targeting agents was prepared by using PEG400 and Twenn80 ( 17 , 18 ).…”

Section: Methodsmentioning

confidence: 99%

MDM2 Binding Protein Induces the Resistance of Hepatocellular Carcinoma Cells to Molecular Targeting Agents via Enhancing the Transcription Factor Activity of the Pregnane X Receptor

Jiang

Han³

et al. 2021

Front. Oncol.

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The MDM2 binding protein (MTBP) has been considered an important regulator of human malignancies. In this study, we demonstrate that the high level of MTBP’s endogenous expression is correlated with poor prognosis of advanced hepatocellular carcinoma (HCC) patients who received sorafenib. MTBP interacted with the Pregnane X receptor (PXR) and enhanced the transcription factor activity of PXR. Moreover, MTBP enhanced the accumulation of PXR in HCC cells’ nuclear and the recruitment of PXR to its downstream gene’s (cyp3a4’s) promoter region. Mechanically, the knockdown of MTBP in MHCC97-H cells with high levels of MTBP decelerated the clearance or metabolism of sorafenib in HCC cells and led to the resistance of HCC cells to sorafenib. Whereas overexpression of MTBP in in MHCC97-L cells with low levels of MTBP showed the opposite trend. By establishing the interaction between MTBP and PXR, our results indicate that MTBP could function as a co-activator of PXR and could be a promising therapeutic target to enhance the sensitivity of HCC cells to molecular targeting agents.

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Hsa-miR-4271 downregulates the expression of constitutive androstane receptor and enhances in vivo the sensitivity of non-small cell lung cancer to gefitinib

Cited by 29 publications

References 59 publications

TPX2 Enhanced the Activation of the HGF/ETS-1 Pathway and Increased the Invasion of Endocrine-Independent Prostate Carcinoma Cells

TPX2 Enhanced the Activation of the HGF/ETS-1 Pathway and Increased the Invasion of Endocrine-Independent Prostate Carcinoma Cells

miR-27-3p Enhances the Sensitivity of Triple-Negative Breast Cancer Cells to the Antitumor Agent Olaparib by Targeting PSEN-1, the Catalytic Subunit of Γ-Secretase

MDM2 Binding Protein Induces the Resistance of Hepatocellular Carcinoma Cells to Molecular Targeting Agents via Enhancing the Transcription Factor Activity of the Pregnane X Receptor

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