Expression of MicroRNA-325-3p and its potential functions by targeting HMGB1 in non-small cell lung cancer

Yao, Shihua; Zhao, Tiejun; Jin, Hai

doi:10.1016/j.biopha.2015.01.013

Cited by 42 publications

(46 citation statements)

References 25 publications

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“…To explore the mechanism of the up‐regulation of KIF2C in NSCLC, we searched TargetScan database for potential regulatory miRs. Among the candidates, miR‐325‐3p attracted our attention, for that it has been reported to be down‐regulated in NSCLC (Figure A). We demonstrated that the transfection of miR‐325‐3p into A549 and H226 cells resulted in a profound reduction of KIF2C expression at both mRNA and protein levels, while miR‐325‐3p had opposite effects (Figure B,C), which indicated the negative regulation of KIF2C by miR‐325‐3p.…”

Section: Resultsmentioning

confidence: 99%

“…Limited studies showed its function of regulating pituitary secretion and circadian rhythms . A recent study demonstrated that it was decreased in NSCLC patients, and patients with low expression level of it had significantly shorter overall survival time . In this study, we identified KIF2C was a novel target gene of miR‐325‐3p, which helps elucidate the mechanism that miR‐325‐3p inhibits the progression of NSCLC.…”

Section: Discussionmentioning

confidence: 99%

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KIF2C exerts an oncogenic role in nonsmall cell lung cancer and is negatively regulated by miR‐325‐3p

Gan

Lin

et al. 2019

Cell Biochemistry & Function

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Nonsmall cell lung cancer (NSCLC) is one of the leading causes of cancer‐related death worldwide. Kinesin family member 2C (KIF2C), a modulator in microtubule depolymerization, bipolar spindle formation, and chromosome segregation, has been reported to take roles in cancer biology, but its role in NSCLC remains unclear. This study was intended to investigate the expression and function of KIF2C in NSCLC. Our results demonstrated that KIF2C was up‐regulated in NSCLC tissues and cell lines. The high expression of KIF2C in NSCLC tissues was significantly correlated with higher T stage (0.0078), worse differentiation status (0.0049), and lymph node metastasis (P < .0001). We also proved that the high expression level of KIF2C predicted worse prognosis of the patients. After knockdown of KIF2C, the proliferation and metastasis of NSCLC cells were inhibited. Luciferase reporter assay suggested that KIF2C was a target gene of miR‐325‐3p, which was reported to be a tumour suppressor in NSCLC. In conclusion, this study proved an oncogenic role of KIF2C in NSCLC and partly clarified the mechanism of its high expression. Our findings provided a useful insight into the mechanism of NSCLC progression and offered clues to novel therapy strategies.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

KIF2C exerts an oncogenic role in nonsmall cell lung cancer and is negatively regulated by miR‐325‐3p

Gan

Lin

et al. 2019

Cell Biochemistry & Function

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“…HMGB1 is present at increased levels in NSCLC patients [46]. HMGB1-mediated autophagy has been reported to contribute to acquired NSCLC chemo-resistance [30, 31].…”

Section: Discussionmentioning

confidence: 99%

MiR-142-3p Overexpression Increases Chemo-Sensitivity of NSCLC by Inhibiting HMGB1-Mediated Autophagy

Chen

Zhou

Qiao

et al. 2017

Cell Physiol Biochem

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Background: Non-small-cell lung cancer (NSCLC) is a deadly cancer with high mortality rate. Drug resistance represents a main obstacle in NSCLC treatment. High mobility group box-1 (HMGB1) protein promotes drug resistance in NSCLC cells by activating protective autophagy. Methods: In the current study, we investigated the regulatory role of microRNA-142-3p (miR-142-3p) in HMGB1-mediated autophagy of NSCLC cells and its impact on drug resistance of NSCLC in vitro and in vivo. HMGB1 was identified as a putative target gene of miR-142-3p by in silico analysis. Our luciferase reporter assay results confirmed that miR-142-3p directly targets the 3’-UTR of HMGB1 in NSCLC cells. Results: MiR-142-3p overexpression suppressed while miR-142-3p knockdown increased HMGB1 mRNA and protein expression. Starvation induced HMGB1 expression and activated autophagy in NSCLC cells. The starvation-induced autophagy was inhibited by miR-142-3p overexpression or HMGB1 knockdown. Moreover, miR-142-3p overexpression or HMGB1 knockdown increased PI3K, Akt, and mTOR phosphorylation. Inhibition of PI3K or mTOR restored starvation-induced autophagy inhibited by miR-142-3p overexpression or HMGB1 knockdown. Conclusions: These results demonstrated that miR-142-3p regulates starvation-induced autophagy of NSCLC cells by directly downregulating HMGB1 and subsequently activating the PI3K/Akt/mTOR pathway. Further, miR-142-3p overexpression inhibited anticancer drug-induced autophagy and increased chemo-sensitivity of NSCLC in vitro and in vivo. These findings shed light on the therapeutic potential of miR-142-3p in combating acquired NSCLC chemo-resistance.

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“…Recently, microRNA-325-3p [21] and MiRNA-218 [22], as the new regulators of HMGB1, regulated cell invasion and proliferation by targeting HMGB1 in non-small cell lung cancer. Zhang et al [23] found that HMGB1 and NF-kappaB p65 protein expression showed a positive correlation, and HMGB1 and NF-kappaB p65 expression might be related to non-small cell lung cancer metastasis.…”

Section: Introductionmentioning

confidence: 99%

Interference with HMGB1 increases the sensitivity to chemotherapy drugs by inhibiting HMGB1-mediated cell autophagy and inducing cell apoptosis

Zhang

Wang

et al. 2015

Tumor Biol.

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Non-small cell lung cancer is commonly seen with higher morbidity and mortality. High-mobility group protein 1 (HMGB1) is a highly conserved nuclear protein, which is involved in multiple human diseases including cancers. However, the mechanisms of HMGB1 in non-small cell lung cancer remain unclear. The goal of the present study is to identify the relationship between HMGB1 and the progresssion of non-small cell lung cancer and investigate the molecular mechanism of HMGB1 in non-small lung cancer cell lines. Firstly, we detected the expression levels of HMGB1 by by real-time PCR and western blotting analysis, and the results demonstrated that HMGB1 was much higher expressed in non-small cell lung cancer cell lines, including A549, SPC-1-1, NCI-2170, SK-MES-1, and NCI-H1299, compared with that of WI-38. Next, 5 μM of adriamycin (AMD), 20 μM of cisplatin (DDP), and 50 μM of methotrexate (MTX) were used to treat A549 cells and SPC-A-1 cells for 48 h. The results showed that treatment with chemotherapy drugs significantly increased the levels of HMGB1 in A549 cells and SPC-A-1 cells. Moreover, the expression levels of HMGB1 increased in a time-dependent manner being treated with DDP. Then, the endogenous HMGB1 expression was successfully interferred with shRNA specific to HMGB1 in A549 and SPC-A-1 cells, which was detected by western blotting analysis. Then, the cisplatin-sensitive A549 cells and cisplatin-resistant A549/DDP cells were treated with increasing concentrations of cisplatin for 24, 48, and 72 h; cell viability were analyzed by MTT assay; and IC50 values were calculated. The results demonstrated that the expression level of HMGB1 in A549/DDP cells was much higher than that of A549 cells; moreover, transfection with HMGB1 shRNA in A549/DDP cells decreased the IC50 value of cisplatin in A549/DDP cells. The expression levels of autophagy-related proteins beclin-1 and LC3-II were significantly higher in A549/DDP cells or the A549 cells treated with chemotherapeutic drugs, compared with that in A549 cells. However, interference with endogenous HMGB1 obviously suppressed autophagy-related proteins and increased cell apoptosis rate and the expression of cleaved caspase-3 in A549/DDP cells. All of the data suggested that interference with the endogenous HMGB1 significantly inhibited cell autophagy and increased cell apoptosis of A549/DDP cells. Thus, the study on the resistance of chemotherapy drugs would provide a theoretical reference for clinical treatment of non-small cell lung cancer.

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Expression of MicroRNA-325-3p and its potential functions by targeting HMGB1 in non-small cell lung cancer

Cited by 42 publications

References 25 publications

KIF2C exerts an oncogenic role in nonsmall cell lung cancer and is negatively regulated by miR‐325‐3p

KIF2C exerts an oncogenic role in nonsmall cell lung cancer and is negatively regulated by miR‐325‐3p

MiR-142-3p Overexpression Increases Chemo-Sensitivity of NSCLC by Inhibiting HMGB1-Mediated Autophagy

Interference with HMGB1 increases the sensitivity to chemotherapy drugs by inhibiting HMGB1-mediated cell autophagy and inducing cell apoptosis

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