Role of microRNA-21 in radiosensitivity in non-small cell lung cancer cells by targeting PDCD4 gene

Jiang, Li-Peng; He, Chufeng; Zhu, Zhou

doi:10.18632/oncotarget.15644

Cited by 45 publications

(33 citation statements)

References 42 publications

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“…Studies show that miRNA molecules such as miR-181a and miR-140-5p are important in autophagy regulation (19,20). It is reported that miR-21 is able to regulate the drug resistance of NSCLC (21). Therefore, it is hypothesized that miR-21 may participate in the occurrence and development of NSCLC by regulating autophagy.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑21 promotes the proliferation, migration and invasion of non‑small cell lung cancer A549 cells by regulating autophagy activity via AMPK/ULK1 signaling pathway

Zeng

et al. 2018

Exp Ther Med

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Abstract. The present study investigated the expression of microRNA (miR)-21 in non-small cell lung cancer (NSCLC) tissues, its biological functions and mechanism of autophagy regulation. A total of 46 patients with NSCLC were enrolled in the present study. To measure the expression of miR-21, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was employed. NSCLC A549 cells were transfected with miR-negative control (NC), miR-21 mimics or inhibitor. The CCK-8 assay was used to investigate the proliferation of A549 cells. To study migration and invasion abilities of A549 cells, The Transwell assay was performed. In addition, to determine the expression levels of ULK1, LC3B, AMPKα, p-AMPKα and p62 proteins, western blotting was conducted and laser confocal microscopy was performed to observe the formation of autophagosomes in A549 cells. To explore whether miR-21 regulates the biological functions of A549 cells via autophagy, an autophagy inhibitor, 3-MA, or agonist, rapamycin, were used in a rescue assay. Results indicated that miR-21 expression in NSCLC tissues was enhanced, and closely correlated with the occurrence and development of NSCLC. In vitro experiments showed that miR-21 mimics promoted the proliferation, migration and invasion of A549 cells, while miR-21 inhibitor inhibited these biological functions. Western blotting indicated that miR-21 upregulated autophagy marker LC3BⅡ protein, but downregulated p62 protein. Laser confocal microscopy showed that miR-21 activated autophagy of A549. Rescue experiments indicated that autophagy reversed the effect of miR-21 on the proliferation, migration and invasion of A549 cells. Western blotting data suggested that autophagy-related AMPK/ULK1 signaling pathway was activated by miR-21, and interference or overexpression of ULK1 reversed the biological functions of miR-21. The present study demonstrated that miR-21 expression in NSCLC tissues was upregulated and positively correlated with lymphatic metastasis and clinical staging. In addition, miR-21 regulated autophagy activity of NSCLC A549 cells via AMPK/ULK1 signaling pathway, and promoted the proliferation, migration and invasion of NSCLC A549 cells.

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Section: Introductionmentioning

confidence: 99%

MicroRNA‑21 promotes the proliferation, migration and invasion of non‑small cell lung cancer A549 cells by regulating autophagy activity via AMPK/ULK1 signaling pathway

Zeng

et al. 2018

Exp Ther Med

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“…Downregulation of PDCD4 is associated with a poor prognosis. miRNAs, such as miR-21 and miR-183, target PDCD4 (6,30,41). In this study, the importance of miR-96 was revealed by microarray analysis of clinical samples, where miR-96 was demonstrated to be upregulated in GBM cases compared with normal tissues (Fig.…”

Section: Discussionmentioning

confidence: 70%

“…1A). Therefore, the miR-96 expression was further analyzed in an array of GBM cell lines (U87-MG, U251-MG, A172 and T98g), which have been reported to have varying radiosensitivity (30). As illustrated in Fig.…”

Section: Reverse Transcription-quantitative Polymerase Chain Reactionmentioning

confidence: 99%

“…The downregulation of PDCD4 in GBM is partly due to epigenetic silencing secondary to 5'cytosine-phosphate-guanine island methylation (28). Overexpression of miR-21 has been reported to target PDCD4 mRNA for degradation (29,30). Although several studies have examined PDCD4 in glioma, the detailed molecular mechanisms underlying the role of PDCD4 in GBM remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

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Upregulation of miR-96 promotes radioresistance in glioblastoma cells via targeting PDCD4

Guo

Tian

et al. 2018

Int J Oncol

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Glioblastoma multiforme (GBM) is the most deadly brain tumor, and it is characterized by extremely poor therapeutic response and overall survival. Adjuvant radiotherapy remains the standard of care following surgical resection. Thus, elucidating the mechanisms conferring radioresistance in GBM is extremely urgent. In the present study, miR-96 was demonstrated to be significantly upregulated in radioresistant GBM cells. Knockdown of miR-96 in the radioresistant GBM cells T98G elevated the % of apoptotic cells and reduced their clonogenic formation ability following radiotherapy. By contrast, overexpression of miR-96 in the radiosensitive GBM cells U87-MG reduced the % of apoptotic cells and increased their clonogenic formation ability following radiotherapy. Results from phosphorylated-H2A histone family member X (γH2AX) foci staining and comet assays revealed that miR-96 enhanced the DNA repair processes. Furthermore, miR-96 overexpression conferred radioresistance by downregulating programmed cell death protein 4 (PDCD4). Luciferase assay results revealed that miR-96 bound to the 3'UTR of PDCD4 mRNA. Finally, U87-MG cells regained radiosensitivity following PDCD4 overexpression. Taken together, the present is the first study to establish that upregulation of miR-96 in GBM cells confers radioresistance via targeting PDCD4, which might be a potential therapeutic target for GBM.

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“…14 In terms of downregulation of proteins, miRNA-21 has been reported to specifically target tumor suppressors such as PTEN, 15 Bcl-2, 15 Smad7, 16 and PDCD4. 17 Long non-coding RNAs (lncRNAs) play crucial roles in many diseases via controlling gene expression. 18 One of their mechanisms of action involves the formation of regulatory networks with other RNA species, such as miRNAs and mRNAs.…”

Section: Introductionmentioning

confidence: 99%

<p>Up-Regulation of MicroRNA-21 Indicates Poor Prognosis and Promotes Cell Proliferation in Esophageal Squamous Cell Carcinoma via Upregulation of lncRNA SNHG1</p>

Dong-bo¹,

Huang²,

Lv³

et al. 2020

CMAR

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Introduction: MicroRNA-21 (miRNA-21) and lncRNA SNHG1 (small nucleolar RNA host gene 1) are known to be aberrantly upregulated and promote tumor progression in various cancers. Nevertheless, very few studies have determined the roles of tissue and circulating miRNA-21 and SNHG1 in ESCC patients. Particularly, knowledge about the characteristics of miRNA-21 and SNHG1 expression and their correlations with survival rates, as well as their interaction with each other remains inadequate in ESCC. Methods: Thse expression level of miRNA-21 and SNHG1 of tissues, serum and cell lines were detected by qRT-PCR, and the characteristics of their expression and clinicopathology were analyzed. Then, the diagnostic and prognosis value of serum and tissue miRNA-21 and SNHG1 were evaluated, respectively. In addition, the interaction with each other between miRNA-21 and SNHG1, as well as the effect on ESCC cell proliferation were further clarified. Results: The expression level of miRNA-21 and SNHG1 are significantly upregulated in tissues, serum and cell lines of ESCC, and tissue miRNA-21 and SNHG1 significantly correlates with lymph node metastasis, TNM stage, tumor size, and poor overall survival in ESCC patients. The receiver operating characteristic (ROC) curves show that areas under the ROC curve (AUC) for serum miRNA-21 and SNHG1 are 0.928 and 0.850, respectively. Pearson correlation coefficient indicated that the expression levels of miRNA-21 and SNHG1 in frozen cancerous tissues are significantly associated with their respective serum levels. Further, Cox univariate and multivariate analyses reveal that miRNA-21 and SNHG1 are independent prognostic factors for overall survival (OS) and disease-free survival (DFS) in ESCC patients. In addition, our in vitro data revealed a novel regulatory pathway, in which miRNA-21 is probably a unidirectional upstream positive regulator of SNHG1 in ESCC cells, and the interaction between miRNA-21 and SNHG1 plays an important role in the proliferation of ESCC cells. Discussion: In summary, our data show that SNHG1 may be a novel downstream target of miRNA-21 and not vice versa in ESCC cells and contributes significantly toward the proliferation of ESCC cells. These findings suggest that miRNA-21 and SNHG1 may serve as potential diagnostic, prognostic biomarkers and therapeutic targets for ESCC patients.

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Role of microRNA-21 in radiosensitivity in non-small cell lung cancer cells by targeting PDCD4 gene

Cited by 45 publications

References 42 publications

MicroRNA‑21 promotes the proliferation, migration and invasion of non‑small cell lung cancer A549 cells by regulating autophagy activity via AMPK/ULK1 signaling pathway

MicroRNA‑21 promotes the proliferation, migration and invasion of non‑small cell lung cancer A549 cells by regulating autophagy activity via AMPK/ULK1 signaling pathway

Upregulation of miR-96 promotes radioresistance in glioblastoma cells via targeting PDCD4

<p>Up-Regulation of MicroRNA-21 Indicates Poor Prognosis and Promotes Cell Proliferation in Esophageal Squamous Cell Carcinoma via Upregulation of lncRNA SNHG1</p>

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