HMGB1 induces the overexpression of miR-222 and miR-221 and increases growth and motility in papillary thyroid cancer cells

Mardente, Stefania; Mari, Emanuela; Consorti, Fabrizio; Gioia, Cira Di; Negri, Rodolfo; Etna, Marilena P.; Zicari, Alessandra; Antonaci, A

doi:10.3892/or.2012.2058

Cited by 71 publications

(60 citation statements)

References 20 publications

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“…It has been reported that HMGB1 has a postive correlation with inflammatory responses and various cancer progression [23]. Meanwhile, HMGB1 is proved to be the target of miRNAs [25], such as miR-200c, or regulate some miRNA including miR-222 and miR-221 [26] to inhibit or promote the invision and metastasis of various tumor cells. In the present study, we explored the molecular mechanism of HMGB1 in nonsmall cell lung cancer cells and explored the role of HMGB1 in tumorigenesis and progression of lung cancers.…”

Section: Autophagy Is Detected In Ddp-resistant Cells A549/ddp or A54mentioning

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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Section: Autophagy Is Detected In Ddp-resistant Cells A549/ddp or A54mentioning

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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“…Higher expression levels of those miRs were detected in cancers presenting with capsular and vascular invasion or lymph node metastasis (51). OncomiRs miR-221 and miR-222 were reported to play a role in PTC aggressiveness (52) and, in the Cancer Genome Atlas (TCGA) data, were associated with less-differentiated tumors (47). In TCGA data, a more aggressive phenotype of thyroid cancer was also correlated with overexpression of miR-21 and miR-146b, as well as the loss of miR-204 (47).…”

Section: Micrornas In Cancer Prognosticsmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: MicroRNA in diagnostics and therapy of thyroid cancer

Wójcicka

Kolanowska

Jażdżewski

2016

European Journal of Endocrinology

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MicroRNAs, short non-coding regulators of the gene expression, are subjects of numerous investigations assessing their potential use in the diagnostics and management of human diseases. In this review, we focus on studies that analyze the utility of microRNAs as novel diagnostic and therapeutic tools in follicular cell-derived thyroid carcinomas. This very interesting and promising field brings new insight into future strategies for personalized medicine.

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“…Similarly, the present study reports that HMGB1 has an effect on neuroblastoma cell lines by enhancing miR-221 and -222 expression in both MYCN-amplified and non-amplified cell lines. The growth increase induced by HMGB1 in SK-N-BE(2) cells may be explained by the known association between N-Myc transcription factor and HMGB1, which acts on AKT-activating pathways (22). Furthermore, the present study showed that HMGB1 enhances miR-221/222 expression and induces growth in SK-N-BE(2) cells.…”

Section: Discussionmentioning

confidence: 49%

Action of HMGB1 on miR-221/222 cluster in neuroblastoma cell lines

et al. 2016

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Abstract. microRNA (miR/miRNA) are small non-coding RNAs that control gene expression at the post-transcriptional level by targeting mRNAs. Aberrant expression of miRNAs is often observed in different types of cancer. Specific miRNAs function as tumor suppressors or oncogenes and interfere with various aspects of carcinogenesis, including differentiation, proliferation and invasion. Upregulation of miRNAs 221 and 222 has been shown to induce a malignant phenotype in numerous human cancers via inhibition of phosphatase and tensin homolog (PTEN) expression. Neuroblastoma is the most common extracranial solid malignancy in children, which is characterized by cellular heterogeneity that corresponds to different clinical outcomes. The different cellular phenotypes are associated with different gene mutations and miRs that control genetic and epigenetic factors. For this reason miRs are considered a potential therapeutic target in neuroblastoma. The aim of the present study was to investigate the mechanisms by which extracellular high mobility group box 1 (HMGB1) promotes cell growth in neuroblastoma. SK-N-BE(2) and SH-SY5Y neuroblastoma derived cell lines were transfected with the antisense oligonucleotides, anti-miR-221 and -222, followed by treatment with HMGB1 to investigate the expression of the oncosuppressor PTEN. In this study, it was demonstrated that HMGB1, which is released by damaged cells and tumor cells, upregulates miR-221/222 oncogenic clusters in the two human neuroblastoma derived cell lines. The results revealed that the oncogenic cluster miRs 221/222 were more highly expressed by the most undifferentiated cell line [SK-N-BE (2)] compared with the the less tumorigenic cell line (SH-SY5Y) and that exogenous HMGB1 increases this expression. In addition, HMGB1 modulates PTEN expression via miR-221/222, as demonstrated by transiently blocking miR-221/222 with anti-sense oligonucleotides. These results may lead to the development of novel therapeutic strategies for neuroblastoma.

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HMGB1 induces the overexpression of miR-222 and miR-221 and increases growth and motility in papillary thyroid cancer cells

Cited by 71 publications

References 20 publications

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

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

MECHANISMS IN ENDOCRINOLOGY: MicroRNA in diagnostics and therapy of thyroid cancer

Action of HMGB1 on miR-221/222 cluster in neuroblastoma cell lines

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