Methylation-mediated repression of microRNA-129-2 suppresses cell aggressiveness by inhibiting high mobility group box 1 in human hepatocellular carcinoma

Liu, Zhikui; Dou, Changwei; Yao, Bowen; Xu, Meng; Ding, Linglong; Wang, Yufeng; Jia, Yuli; Li, Qing; Zhang, Hongyong; Tu, Kangsheng; Song, Tao; Liu, Qingguang

doi:10.18632/oncotarget.9377

Cited by 53 publications

(51 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further investigation revealed that overexpression of HMGB1 impaired the suppressive effects of miR-34a on the CSCC cell proliferation, migration and invasion, which confirms this speculation. In addition, certain other miRs have also been demonstrated to directly target HMGB1, including miR-142 (23), miR-126 (24), miR-181 (25), miR-218 (26), miR-129 (27), miR-24 (28) and miR-141 (29). Therefore, the findings of the present study further expand the understanding of the regulatory mechanism of miRs/HMGB1 signaling in human cancer.…”

Section: Discussionsupporting

confidence: 55%

MicroRNA‑34a directly targets high‑mobility group box 1 and inhibits the cancer cell proliferation, migration and invasion in cutaneous squamous cell carcinoma

Luo

Zhou

et al. 2017

Exp Ther Med

View full text Add to dashboard Cite

Abstract. Cutaneous squamous cell carcinoma (CSCC) is the second most common type of skin cancer with increasing incidence. In recent years, several microRNAs (miRs) have been demonstrated to serve an oncogenic or tumor suppressive role in CSCC. However, the exact role of miR-34a in CSCC and the underlying regulatory mechanism remain unclear. The present study aimed to investigate the regulatory mechanism of miR-34a in the malignant phenotypes of CSCC cells using MTT assay, wound healing assay and transwell assay. It was observed that miR-34a was significantly downregulated in CSCC tissues and cell lines, and low miR-34a expression was associated with the aggressive progression of CSCC. Restoration of miR-34a significantly suppressed the proliferation, migration and invasion of CSCC SCL-1 cells. High-mobility group box 1 (HMGB1) was then identified as a target gene of miR-34a in SCL-1 cells using bioinformatics prediction. The expression of HMGB1 was significantly upregulated in the CSCC tissues and cell lines. Furthermore, the protein expression of HMGB1 was negatively regulated by miR-34a in SCL-1 cells, while overexpression of HMGB1 impaired the inhibitory effects of miR-34a on SCL-1 cells. These findings suggest that miR-34a represses the malignant phenotypes of CSCC cells, at least partly, via the inhibition of HMGB1. Therefore, miR-34a may be used as a promising therapeutic candidate for CSCC.

show abstract

Section: Discussionsupporting

confidence: 55%

MicroRNA‑34a directly targets high‑mobility group box 1 and inhibits the cancer cell proliferation, migration and invasion in cutaneous squamous cell carcinoma

Luo

Zhou

et al. 2017

Exp Ther Med

View full text Add to dashboard Cite

show abstract

“…Numerous studies have demonstrated that aberrant miRNAs are involved in cancer initiation, development and progression (22,23), including cervical cancer (CC). miRNAs have been identified as novel prognostic biomarkers and effective therapeutic targets of CC.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-1297 inhibits metastasis and epithelial-mesenchymal transition by targeting AEG-1 in cervical cancer

Wang

Guo

et al. 2017

Oncology Reports

View full text Add to dashboard Cite

Abstract. Accumulating evidence has demonstrated that aberrant miRNAs contribute to cervical cancer (CC) development and progression. However, the roles of various miRNAs in CC remain to be determined. In the present study, we confirmed that a decreased miR-1297 expression was present in CC tissues and cell lines. Our clinical analysis revealed that the downregulated miR-1297 expression was significantly correlated with poor prognostic features including lymph node metastasis and lymphovascular space invasion. Moreover, we confirmed that miR-1297 was a novel independent prognostic marker for predicting the 5-year survival of CC patients. The ectopic overexpression of miR-1297 inhibited cell migration, invasion and EMT progression, while downregulated miR-1297 reversed these effects. In addition, miR-1297 regulated AEG-1 by directly binding to its 3'-UTR. In clinical samples of CC, miR-1297 was inversely correlated with AEG-1, which was upregulated in CC. Alteration of AEG-1 expression at least partially abolished the migration, invasion and EMT progression effects of miR-1297 on CC cells. In conclusion, our results indicated that miR-1297 functioned as a tumor suppressor gene in regulating the EMT and metastasis of CC via targeting of AEG-1, and may represent a novel potential therapeutic target and prognostic marker for CC.

show abstract

“…QRT-PCR was conducted as reported previously [35, 36]. All RNA was extracted based on the protocol of TRIzol reagent (Invitrogen, Carlsbad, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Then applying the biotinylated secondary antibodies (Goldenbridge, Zhongshan,China) according to SP-IHC assays.. Specific experiment was conducted similar to previously reported [35, 36]. …”

Section: Methodsmentioning

confidence: 99%

Hypoxia Accelerates Aggressiveness of Hepatocellular Carcinoma Cells Involving Oxidative Stress, Epithelial-Mesenchymal Transition and Non-Canonical Hedgehog Signaling

Liu¹,

Tu²,

Wang³

et al. 2017

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

Background/Aims: Hypoxic microenvironment, a common feature of hepatocellular carcinoma (HCC), can induce HIF-1α expression and promote the epithelial-mesenchymal transition (EMT) and invasion of cancer cells. However, the underlying molecular mechanisms have not fully elucidated. Methods: HCC cells were cultured under controlled hypoxia conditions or normoxic conditions. Transwell assays were used to examine the migration and invasion capacity. HIF-1α siRNA, cyclopamine (a SMO antagonist) and GLI1 siRNA were used to inhibit HIF-1α transcription or Hh signaling activation. Results: In present study, we first observed a strongly positive correlation between HIF-1α and GLI1 expression in HCC tissues. Then, we showed that hypoxia significantly promoted EMT process and invasion of HCC cells, associated with activating the non-canonical Hh pathway without affecting SHH and PTCH1 expression. HIF-1α knockdown mitigated hypoxia-induced SMO and GLI1 expression, EMT invasion of HCC cells. Moreover, the SMO inhibitor or GLI1 siRNA also reversed the hypoxia-driven EMT and invasion of HCC cells under hypoxia condition. Here, we show that non-canonical Hh signaling is required as an important role to switch on hypoxia-induced EMT and invasion in HCC cells. In addition, we found that hypoxia increased ROS production and that ROS inhibitors (NAC) blocked GLI1-dependent EMT process and invasion under hypoxic conditions. To determine a major route of ROS production, we tested whether nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) is involved in hypoxia-induced ROS production. NOX4 expression was found to be increased at both mRNA and protein levels in hypoxic HCC cells. Furthermore, siRNA-mediated knockdown of NOX4 expression abolished hypoxia induced ROS generation and GLI1-dependent activation and invasion of HCC cells. Conclusion: Our findings indicate that hypoxia triggers ROS-mediated GLI1-dependent EMT progress and invasion of HCC cells through induction of NOX4 expression. Thus, hypoxia-driven ROS mediated non-canonical Hh signaling may play an important role in the initiation of EMT and provides a potential marker for cancer prevention and treatment.

show abstract

Methylation-mediated repression of microRNA-129-2 suppresses cell aggressiveness by inhibiting high mobility group box 1 in human hepatocellular carcinoma

Cited by 53 publications

References 43 publications

MicroRNA‑34a directly targets high‑mobility group box 1 and inhibits the cancer cell proliferation, migration and invasion in cutaneous squamous cell carcinoma

MicroRNA‑34a directly targets high‑mobility group box 1 and inhibits the cancer cell proliferation, migration and invasion in cutaneous squamous cell carcinoma

MicroRNA-1297 inhibits metastasis and epithelial-mesenchymal transition by targeting AEG-1 in cervical cancer

Hypoxia Accelerates Aggressiveness of Hepatocellular Carcinoma Cells Involving Oxidative Stress, Epithelial-Mesenchymal Transition and Non-Canonical Hedgehog Signaling

Contact Info

Product

Resources

About