The NKD1/Rac1 feedback loop regulates the invasion and migration ability of hepatocarcinoma cells

Li, Jie; Zhang, Sheng; Hu, Qing; Zhang, Kang; Jin, Jianbin; Zheng, Xuqing; Yin, Zhenyu; Wang, Xiaomin

doi:10.1038/srep26971

Cited by 18 publications

(12 citation statements)

References 31 publications

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“…However, the underlying molecular mechanism of NKD1 in osteosarcoma cell invasion and migration remains unidentified. Recently, Li et al () showed that forced expression of NKD1 inhibited HCC cell migration and invasion in vivo and in vitro, which was inconsistent with our observations. They found that NKD1‐mediated regulation of HCC cell invasion and migration is dependent on Rac1.…”

Section: Discussioncontrasting

confidence: 99%

MicroRNA‐195‐5p suppresses osteosarcoma cell proliferation and invasion by suppressing naked cuticle homolog 1

Chu

Wang

2017

Cell Biology International

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MiR-195-5p has been shown to play an essential role in human cancer progression. Nevertheless, the biological role of miR-195-5p in osteosarcoma development remains unclear. In this study, real-time PCR was performed to examine the miR-195-5p expression in human osteosarcoma cell lines. CCK-8 assay and Transwell assay were carried out to measure the effect of miR-195-5p on cell proliferation and invasion. Luciferase reporter assay was used to identify the targets of miR-195-5p. The results showed that miR-195-5p was significantly downregulated in osteosarcoma cells. Forced expression of miR-195-5p significantly inhibited cell proliferation, suppressed cell migration and invasion, compared with wild-type and control-transfected osteosarcoma cells. Luciferase reporter assay revealed that miR-195-5p binds to the 3'-untranslated region (UTR) of Naked cuticle homolog 1 (NKD1), indicating that NKD1 was a novel target of miR-195-5p. NKD1 mRNA and protein levels were reduced after overexpression of miR-195-5p. Moreover, silencing of NKD1 significantly inhibited the proliferation and invasion of osteosarcoma cells. Accordingly, our results support a tumor suppressor role of miR-195-5p in osteosarcoma through inhibiting NKD1, and it may be a promising therapeutic target for osteosarcoma.

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Section: Discussioncontrasting

confidence: 99%

MicroRNA‐195‐5p suppresses osteosarcoma cell proliferation and invasion by suppressing naked cuticle homolog 1

Chu

Wang

2017

Cell Biology International

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“…Ras‐related C3 botulinum toxin substrate 1 (RAC1) is a pleiotropic regulator of many cellular processes, including the cell cycle, cell‐cell adhesion, motility, and of epithelial differentiation . Recent studies showed that RAC1 worked as an oncogene in many tumors, including breast cancer, melanoma, and liver cancer . In the present study, we for the first time found that RAC1 was a direct target of miR‐365.…”

Section: Discussionsupporting

confidence: 63%

miR‐365 regulates liver cancer stem cells via RAC1 pathway

Jiang

Liu

et al. 2018

Molecular Carcinogenesis

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Liver cancer stem cells (CSCs) were involved in tumorigenesis, progression, recurrence, and drug resistance of hepatocellular carcinoma (HCC). miR-365 was downregulated in hepatocellular carcinoma and inhibited HCC cell proliferation and invasion. However, the role of miR-365 in liver cancer stem cells was unknown. Herein, we observed a remarkable decrease of miR-365 expression in CD133 or EpCAM-positive liver CSCs as well as in CSC-enriched hepatoma spheres. Up-regulated miR-365 suppressed liver CSC expansion by inhibiting the dedifferentiation of hepatoma cells and decreasing the self-renewal ability of liver CSCs. Mechanistically, bioinformatic and luciferase reporter analysis identified Ras-related C3 botulinum toxin substrate 1 (RAC1) as a direct target of miR-365. Overexpression of miR-365 in hepatoma cells downregulated the RAC1 mRNA and protein expression. RAC1 also could promote the expansion of liver CSCs. The special RAC1 inhibitor EHop-106 or RAC1 overexpression abolished the discrepancy in liver CSC proportion and the self-renewal capacity between miR-365 overexpression hepatoma cells and control cells, which further confirmed that RAC1 was required in miR-365-suppressed liver CSCs expansion. miR-365 was downregulated in liver CSCs and could inhibit HCC cells dedifferentiation and liver CSCs expansion by targeting RAC1 signaling.

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“…As such, prevention and treatment of HCC migration and invasion is of great importance for improving the prognosis of HCC patients [19]. EMT plays an important role in the process of metastasis; HCC cells can obtain mesenchymal characteristics though EMT, which enhance their capacity for movement [20].…”

Section: Discussionmentioning

confidence: 99%

CAPZA1 modulates EMT by regulating actin cytoskeleton remodelling in hepatocellular carcinoma

Deng

Cao

Zheng

2017

J Exp Clin Cancer Res

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BackgroundEpithelial-mesenchymal transition (EMT) elicits dramatic changes, including cytoskeleton remodelling as well as changes in gene expression and cellular phenotypes. During this process, actin filament assembly plays an important role in maintaining the morphology and movement of tumour cells. Capping protein, a protein complex referred to as CapZ, is an actin-binding complex that can regulate actin cytoskeleton remodelling. CAPZA1 is the α1 subunit of this complex, and we hypothesized that CAPZA1 regulates EMT through the regulation of actin filaments assembly, thus reducing the metastatic ability of hepatocellular carcinoma (HCC) cells.MethodsImmunohistochemistry was used to detect CAPZA1 expression in 129 HCC tissues. Western blotting and qPCR were used to detect CAPZA1, EMT markers and EMT transcription factors in HCC cells. Transwell migration and invasion assays were performed to observe the migration and invasion of HCC cells. Cell Counting Kit-8 (CCK-8) was used to detect the proliferation of HCC cells. Immunoprecipitation was used to detect the interaction between CAPZA1 and actin filaments. Finally, a small animal magnetic resonance imager (MRI) was used to observe metastases in HCC cell xenografts in the liver.ResultsCAPZA1 expression levels were negatively correlated with the biological characteristics of primary HCC and patient prognosis. CAPZA1 expression was negatively correlated with the migration and invasion of HCC cells. CAPZA1 down regulation promoted the migration and invasion of HCC cells. Conversely, CAPZA1 overexpression significantly inhibited the migration and invasion of HCC cells. Moreover, CAPZA1 expression levels were correlated with the expression of the EMT markers E-cadherin, N-cadherin and Vimentin. Furthermore, the expression of Snail1 and ZEB1 were negatively correlated with CAPZA1 expression levels. Similarly, CAPZA1 significantly inhibited intrahepatic metastases of HCC cells in an orthotopic transplantation tumour model.ConclusionsCAPZA1 inhibits EMT in HCC cells by regulating actin cytoskeleton remodelling, thereby reducing the metastatic ability of the cells. Together, our data suggest that CAPZA1 could be a useful biomarker for clinical determination of the prognosis of HCC patients.

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The NKD1/Rac1 feedback loop regulates the invasion and migration ability of hepatocarcinoma cells

Cited by 18 publications

References 31 publications

MicroRNA‐195‐5p suppresses osteosarcoma cell proliferation and invasion by suppressing naked cuticle homolog 1

MicroRNA‐195‐5p suppresses osteosarcoma cell proliferation and invasion by suppressing naked cuticle homolog 1

miR‐365 regulates liver cancer stem cells via RAC1 pathway

CAPZA1 modulates EMT by regulating actin cytoskeleton remodelling in hepatocellular carcinoma

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