MicroRNA-135b, a HSF1 target, promotes tumor invasion and metastasis by regulating RECK and EVI5 in hepatocellular carcinoma

Li, Yan; Xu, Dan; Bao, Chunyang; Zhang, Yuannv; Chen, Di; Zhao, Fangyu; Ding, Jie; Liang, Linhui; Wang, Qifeng; Liu, Li; Li, Jinjun; Yao, Ming; Huang, Shenglin; He, Xianghuo

doi:10.18632/oncotarget.2965

Cited by 66 publications

(57 citation statements)

References 37 publications

(42 reference statements)

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“…Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) gene expresses in all human normal tissues but is down-regulated in a variety of tumor tissues including liver cancer [1], gastric cancer [2] and colorectal cancer [3]. RECK protein blocks the tumor metastasis and invasion via negative regulation of matrix metalloproteinases (MMPs) [4].…”

Section: Introductionmentioning

confidence: 99%

Suppression of Non-Small Cell Lung Cancer Growth and Metastasis by a Novel Small Molecular Activator of RECK

Shen¹,

Bang-hua²,

Zhang³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Reversion-inducing cysteine-rich protein with kazal motifs (RECK) is a novel tumor suppressor gene that is critical for regulating tumor cell invasion and metastasis. The expression of RECK is dramatically down-regulated in human cancers. Harmine, a tricyclic compound from Peganum harmala, has been shown to have potential anti-cancer activity. Methods: Cell proliferation assay (CCK-8 cell viability assay), cell cycle analysis (detection by flow cytometry), apoptosis staining assay (TUNEL staining), cell migration assay and invasion assay (transwell assay) were carried out to investigate the Harmine’s efficacy on non-small cell lung cancer (NSCLC) cells in vitro. A549-luciferase cell orthotropic transplantation xenograft mouse model was used to determine the effect of Harmine treatment on NSCLC in vivo. Western blotting analysis of cell growth and metastasis related signal pathways was conducted to investigate the molecular mechanism of Harmine’s inhibitory effect on NSCLC. Results: Harmine treatment effectively inhibited cell proliferation and induced the G1/S cell cycle arrest of NSCLC cells. Further study proved that Harmine treatment led to apoptosis induction. Furthermore, treatment with NSCLC cells with Hamine resulted in decreased cell migration and cell invasion in vitro. More importantly, Harmine treatment significantly suppressed the NSCLC tumor growth and metastasis in mouse xenograft model in vivo. Mechanistically, in Harmine-treated NSCLC cells, RECK expression and its downstream signaling cascade were dramatically activated. As a consequence, the expression level of MMP-9 and E-cadherin were significantly decreased. Conclusion: These findings identify Harmine as a promising activator of RECK signaling for metastatic NSCLC treatment.

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Section: Introductionmentioning

confidence: 99%

Suppression of Non-Small Cell Lung Cancer Growth and Metastasis by a Novel Small Molecular Activator of RECK

Shen¹,

Bang-hua²,

Zhang³

et al. 2018

Cell Physiol Biochem

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“…miR-135b has long been regarded as an oncogenic miRNA in different cancer types (3,(31)(32)(33). In the present study, the expression level of miR-135b was significantly higher in lung adenocarcinoma samples than that in corresponding non-cancerous tissue.…”

Section: Mir-135b Expression Status ---------------------------------mentioning

confidence: 44%

Peripheral lung adenocarcinomas harboring epithelial growth factor receptor mutations with microRNA‑135b overexpression are more likely to invade visceral pleura

Wang

Zha

et al. 2017

Oncol Lett

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Abstract. Lung adenocarcinoma, characterized by its early and aggressive local invasion and high metastatic potential, is the most frequently observed histological type of non-small-cell lung cancer (NSCLC). Visceral pleural invasion (VPI) caused by peripheral lung adenocarcinomas is closely associated with the poor prognosis of patients with NSCLC. The association between VPI and some clinicopathological characteristics has been observed in the past few decades. However, the molecular mechanism of VPI in lung adenocarcinomas is unknown. In the present, the expression level of microRNA (miR-)135b and epidermal growth factor receptor (EGFR) mutations using the reverse transcription-quantitative polymerase chain reaction and DNA sequencing, respectively. In addition, the present study aimed at exploring the association between the miR-135b level, EGFR mutations and VPI in peripheral lung adenocarcinoma. The results of the present study demonstrated that miR-135b was significantly upregulated in lung adenocarcinoma compared with adjacent normal tissue and positively associated EGFR mutations in peripheral lung adenocarcinoma. Furthermore, it was identified that lung adenocarcinomas with EGFR mutations and miR-135b overexpression were more likely to invade visceral pleura. Taken together, these findings indicate that miR-135b overexpression is positively associated with mutations to EGFR, which may promote the development of peripheral lung adenocarcinomas by the formation of VPI. This indicates that the two factors may serve as prognostic markers and molecular targets for the treatment of peripheral lung adenocarcinomas.

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“…Among these miRNAs, miR-135b expression is reported to be elevated in many cancers due to the gene mutations (such as gene of Adenomatous Polyposis Coli, APC) [35,36]. Overexpression of miR-135b is found to be involved for cancer progression, metastasis and invasion [37][38][39]. In CRC, studies also demonstrate that miR-135b overexpression is correlated with tumor stage and poor clinical outcome [36].…”

Section: Discussionmentioning

confidence: 99%

Knockdown of Mir-135b Sensitizes Colorectal Cancer Cells to Oxaliplatin-Induced Apoptosis Through Increase of FOXO1

Yan

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Aberrant expression of microRNAs (miRNAs) is found to be responsible for tumorigenesis, cancer development and chemoresistance. Although oxaliplatin is an effective chemotherapeutic drug for treatment of colorectal cancer (CRC), CRC cells can develop some mechanisms to evade oxaliplatin-induced cell death. It is urgent to explore the novel strategies to increase the chemosensitivity of CRC cells. Methods: QRT-PCR analysis was performed to detect the expression of miR-135b in CRC patients’ serum and CRC cell lines. MTT assays were used to evaluate the effect of anti-miR-135b on oxaliplatin-induced cell death in CRC cell lines. Western blot, flow cytometry and luciferase reporter assays were performed to evaluate the potential mechanism and pathway of anti-miR-135b-promoted apoptosis in oxaliplatin-treated CRC cells. Results: Significant upregulation of miR-135b was observed in CRC cell lines and CRC patients’ serum. Knockdown of miR-135b was found to sensitize colorectal cancer cells to oxaliplatin-induced cytotoxicity. Mechanically, knockdown of miR-135b increased the expression level of FOXO1 in CRC. As the downstream, the increased FOXO1 induced by anti-miR-135b promoted the expression of Bim and Noxa. Since Bim and Noxa act as key pro-apoptotic proteins in mitochondrial apoptosis, anti-miR-135b was able to enhance the oxaliplatin-induced apoptosis dependent on the anti-miR-135b/FOXO1 axis. Conclusions: Anti-miR-135b enhanced the anti-tumor effect of oxaliplatin on CRC. Combination with miR-135b antisense nucleotides may represent a novel strategy to sensitize CRC to oxaliplatin-based treatment.

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MicroRNA-135b, a HSF1 target, promotes tumor invasion and metastasis by regulating RECK and EVI5 in hepatocellular carcinoma

Cited by 66 publications

References 37 publications

Suppression of Non-Small Cell Lung Cancer Growth and Metastasis by a Novel Small Molecular Activator of RECK

Suppression of Non-Small Cell Lung Cancer Growth and Metastasis by a Novel Small Molecular Activator of RECK

Peripheral lung adenocarcinomas harboring epithelial growth factor receptor mutations with microRNA‑135b overexpression are more likely to invade visceral pleura

Knockdown of Mir-135b Sensitizes Colorectal Cancer Cells to Oxaliplatin-Induced Apoptosis Through Increase of FOXO1

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