MiR-144 Inhibits Proliferation and Induces Apoptosis and Autophagy in Lung Cancer Cells by Targeting TIGAR

Chen, Shanshan; Li, Ping; Li, Juan; Wang, Yuanyuan; Du, Yuwen; Chen, Xiaonan; Zang, Wenqiao; Wang, Huaqi; Chu, Heying; Zhang, Guojun

doi:10.1159/000369755

Cited by 97 publications

(63 citation statements)

References 41 publications

(41 reference statements)

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“…A previous study found that over-expression of miR-144 suppressed proliferation and promoted apoptosis and autophagy in LC cells by targeting the p53-induced glycolysis and apoptosis regulator, which was consistent with our results [38]. When ERS was inhibited by 4-PBA, the autophagy factors and apoptotic factors also in turn displayed reduced levels.…”

Section: Discussionsupporting

confidence: 92%

Endoplasmic Reticulum Stress Promotes Autophagy and Apoptosis and Reduces Chemotherapy Resistance in Mutant p53 Lung Cancer Cells

Gan

Zhou

Zhong

et al. 2017

Cell Physiol Biochem

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Background/Aims: Lung cancer (LC) continues to be one of the most prevalent cancers around the world. During this study we aimed to investigate the involvement of endoplasmic reticulum stress (ERS) in autophagy, apoptosis, and chemotherapy resistance of mutant p53 LC cells. Methods: Immunohistochemistry was employed to help determine the p53 mutation status of cancer cells from 92 primary LC patients, who were subsequently assigned to either the mutant p53 (n = 39) or wild-type p53 group (n = 53). Results: Mutant p53 cells exhibited increased expression of the C/EBP homologous protein (CHOP), glucose-regulated protein 78 (GRP78), and inositol-requiring enzyme-1α (IRE1α). The Mutant p53 cells were also found to be sensitive to chemotherapy and displayed decreased expression of PI3K, Akt, and mTOR. The mutant p53 cell lines were treated with tunicamycin to induce ERS and rapamycin in order to inhibit mTOR. Both agents increased the expression of CHOP, GRP78, IRE1α, LC3-II/LC3-I, Atg5, Atg7, caspase-3, caspase-12, cleaved caspase-3, cleaved caspase-12, as well as decreases in cell proliferation as well as the expression levels of PI3K, Akt, and mTOR. Enhanced levels of cell apoptosis and reduced chemotherapy resistance were also detected. Conclusion: The findings of our study suggest that ERS promotes autophagy and apoptosis, while acting to reduce chemotherapy resistance in mutant p53 LC cells by downregulating the PI3K/Akt/mTOR signaling pathway.

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Section: Discussionsupporting

confidence: 92%

Endoplasmic Reticulum Stress Promotes Autophagy and Apoptosis and Reduces Chemotherapy Resistance in Mutant p53 Lung Cancer Cells

Gan

Zhou

Zhong

et al. 2017

Cell Physiol Biochem

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“…As lung cancer is associated with the dysregulation of signalling pathways associated with various cellular processes, such as cell cycle progression, cell proliferation and apoptosis, and angiogenesis, researchers have expended considerable effort to identify new agents capable of targeting these pathways as a means of achieving greater therapeutic benefits [8-10]. However, clinical trials have demonstrated that targeting these pathways individually exerts limited effects [11], which may be due to the heterogeneous nature of lung tumours.…”

Section: Introductionmentioning

confidence: 99%

Integrated High Throughput Analysis Identifies GSK3 as a Crucial Determinant of p53-Mediated Apoptosis in Lung Cancer Cells

Zhang¹,

Zhu²,

Sun³

et al. 2017

Cell Physiol Biochem

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Background/Aims: p53 dysfunction is frequently observed in lung cancer. Although restoring the tumour suppressor function of p53 is recently approved as a putative strategy for combating cancers, the lack of understanding of the molecular mechanism underlying p53-mediated lung cancer suppression has limited the application of p53-based therapies in lung cancer. Methods and Results: Using RNA sequencing, we determined the transcriptional profile of human non-small cell lung carcinoma A549 cells after treatment with two p53-activating chemical compounds, nutlin and RITA, which could induce A549 cell cycle arrest and apoptosis, respectively. Bioinformatics analysis of genome-wide gene expression data showed that distinct transcription profiles were induced by nutlin and RITA and 66 pathways were differentially regulated by these two compounds. However, only two of these pathways, 'Adherens junction' and 'Axon guidance', were found to be synthetic lethal with p53 re-activation, as determined via integrated analysis of genome-wide gene expression profile and short hairpin RNA (shRNA) screening. Further functional protein association analysis of significantly regulated genes associated with these two synthetic lethal pathways indicated that GSK3 played a key role in p53-mediated A549 cell apoptosis, and then gene function study was performed, which revealed that GSK3 inhibition promoted p53-mediated A549 cell apoptosis in a p53 post-translational activity-dependent manner. Conclusion: Our findings provide us with new insights regarding the mechanism by which p53 mediates A549 apoptosis and may cast light on the development of more efficient p53-based strategies for treating lung cancer.

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“…In different types of cancers, downregulation of miR-144 has been observed, such as osteosarcoma and mesothelioma, indicating that miR-144 may be a potential tumor suppressor (17,18). Studies have revealed that miR-144 exerts its biologic functions by targeting the 3 0 untranslated region (UTR) of the mRNAs of a number of oncogenes, such as ROCK1 (19), ZEB1 and ZEB2 (20), ADAM (21), TIGAR (22), and c-MET (23). However, whether miR-144 regulates BCL6 in carcinogenesis has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

A Critical Role of miR-144 in Diffuse Large B-cell Lymphoma Proliferation and Invasion

Wang

et al. 2016

Cancer Immunology Research

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MicroRNAs are endogenous noncoding RNAs that play important roles in a wide variety of biologic processes such as apoptosis, development, aging, and tumorigenesis. The B-cell lymphoma 6 (BCL6) transcriptional repressor has emerged as a critical therapeutic target in diffuse large B-cell lymphomas (DLBCL), but the mechanisms regulating BCL6 are still unclear. In the current study, we screened the microRNA expression profiles in DLBCL specimens and cell lines by qRT-PCR and found that the expression of miR-144 was significantly downregulated in DLBCL tissues and cell lines and negatively correlated with BCL6 expression. We further demonstrated that BCL6 was the direct target gene of miR-144, and miR-144 suppressed the expression of BCL6 via binding the 3 0 untranslated region of BCL6 mRNA. Biologically, forced expression of miR-144 significantly attenuated cell proliferation and invasion of OCI-Ly3 cells in vitro, and the tumorsuppressor effect of miR-144 was also confirmed using a xenograft mouse model in vivo. Taken together, our results reveal that miR-144 regulates BCL6 in DLBCL and provide a rationale for developing strategies that target miR-144 as a therapeutic intervention for DLBCL.

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MiR-144 Inhibits Proliferation and Induces Apoptosis and Autophagy in Lung Cancer Cells by Targeting TIGAR

Cited by 97 publications

References 41 publications

Endoplasmic Reticulum Stress Promotes Autophagy and Apoptosis and Reduces Chemotherapy Resistance in Mutant p53 Lung Cancer Cells

Endoplasmic Reticulum Stress Promotes Autophagy and Apoptosis and Reduces Chemotherapy Resistance in Mutant p53 Lung Cancer Cells

Integrated High Throughput Analysis Identifies GSK3 as a Crucial Determinant of p53-Mediated Apoptosis in Lung Cancer Cells

A Critical Role of miR-144 in Diffuse Large B-cell Lymphoma Proliferation and Invasion

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