Tumor suppressor microRNA-34a inhibits cell migration and invasion by targeting MMP-2/MMP-9/FNDC3B in esophageal squamous cell carcinoma

Yang, Lan; Song, Xiaoling; Zhu, Jianbo; Li, Mei; Ji, Yu; Wu, Fei; Chen, Yunzhao; Cui, Xiaobin; Hu, Jianming; Wang, Lianghai; Cao, Yukun; Wei, Yongzhong; Zhang, Wenjie; Li, Feng

doi:10.3892/ijo.2017.4015

Cited by 55 publications

(45 citation statements)

References 59 publications

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“…MMP2 was also found to be implicated in the proliferation of pancreatic and breast cancer cells (38). MMP2 can be targeted by several other microRNAs, such as miR-29b (39) and miR-34a (40), and it was herein verified that miR-93 directly targets MMP2 and plays an important role in NP cells.…”

Section: Discussionsupporting

confidence: 57%

Long non-coding RNA PART1 promotes intervertebral disc degeneration through regulating the�miR‑93/MMP2 pathway in nucleus pulposus cells

2020

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The aim of the present study was to investigate the role of the long non-coding (lnc)RNA PART1 in nucleus pulposus (NP) cells derived from patients with intervertebral disc degeneration (Idd). The level of PART1 in degenerative NP tissues from patients with Idd, bulging and herniated discs was measured by reverse transcription-quantitative PcR (RT-qPcR) analysis. NP cells were isolated from patients with Idd and transfected with siPART1, after which time the growth ability of the NP cells was evaluated by cell counting Kit-8 and colony formation assays, and cell apoptosis was measured by flow cytometry. The levels of the cell proliferation marker Ki-67 and the apoptosis marker cleaved caspase-3, and the levels of genes related to extracellular matrix (EcM) synthesis and degradation, were also evaluated by western blotting and RT-qPcR, as appropriate. Bioinformatics methods predicted that miR-93 was sponged by PART1, and matrix metallopeptidase (MMP)2 was targeted by miR-93, which was further confirmed by dual-luciferase reporter assay. The levels of miR-93 and MMP2 were also measured in NP tissues, and further rescue experiments were performed to confirm the role of the PART1/miR-93/MMP2 pathway in NP cells. PART1 was found to be upregulated in degenerative NP tissues, and siPART1 caused an increase in cell growth ability and EcM synthesis, whereas it decreased cell apoptosis and EcM degradation in NP cells. miR-93 was downregulated and MMP2 was upregulated in degenerative NP tissues. Rescue experiments indicated that the effects of miR-93 inhibitor on NP cells were abolished by siPART1, and the effect of miR-93 mimic on NP cells was rescued by MMP2 overexpression. Thus, the results of the present study demonstrated that PART1 may regulate NP cell degeneration through the miR-93/MMP2 pathway. These findings indicate a novel signaling axis in NP cells that may be explored for the treatment of Idd.

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Section: Discussionsupporting

confidence: 57%

Long non-coding RNA PART1 promotes intervertebral disc degeneration through regulating the�miR‑93/MMP2 pathway in nucleus pulposus cells

2020

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“…Qi Zhang et al reported that MMP2, HEY1 and HES1 together regulate the migration of adipose-derived stem cells and chondrocytes in a coculture system [51]. In tumor studies, MMPs induced tumor invasion and distant metastasis in a variety of tumors, such as breast cancer [52], osteosarcoma [53], endometrial cancer [54], and esophageal squamous cell carcinoma [55]. Therefore, we also studied the correlation between HEY1 and MMPs.…”

Section: Discussionmentioning

confidence: 92%

The NOTCH1-HEY1 pathway regulates self-renewal and epithelial-mesenchymal transition of salivary adenoid cystic carcinoma cells

et al. 2020

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Our previous study demonstrated a close relationship between the NOTCH signaling pathway and salivary adenoid cystic carcinoma (SACC). Its receptor gene, NOTCH1, and its downstream gene, HES1, contribute to the proliferation, invasion and metastasis of SACC. Accumulating evidence supports HEY1 as another effector of the signaling pathway. The purpose of this study was to explore the effects of the NOTCH1-HEY1 pathway on the proliferation, invasion and metastasis of SACC cells. Our results verified that HEY1 is a specific molecular target of the NOTCH signaling pathway in SACC cells and that its expression in carcinoma is much higher than that in paracarcinoma tissues. The expression of NOTCH1 and HEY1 are positively correlated in the salivary adenoid cystic carcinoma tissues. NOTCH1 is significantly related to the activation of HEY1 in SACC, and that HEY1 reciprocally regulates NOTCH1 expression in SACC. HEY1 promotes cell proliferation and spheroid formation and inhibits cell apoptosis in vitro. In addition, HEY1 enhances the tumorigenicity of SACC in vivo. Furthermore, HEY1 increases cell invasion and metastasis by driving the expression of epithelial-mesenchymal transition (EMT)-related genes and MMPs. The results of this study indicate that the NOTCH1-HEY1 pathway is specifically upregulated in SACC and promotes cell proliferation, self-renewal, invasion, metastasis and the expression of EMT-related genes and MMPs. Our findings suggest that a NOTCH1-HEY1 pathway inhibitor might therefore have potential therapeutic applications in treating SACC patients by inhibiting cancer cell growth and metastasis.

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“…44 The effects of microRNAs on matrix metalloproteinases as well as fibronectin type III domain containing 3B expression levels have been studied in the past. 45 In this study, we found that introduction of miR-34a or knockdown of LGR4 can inhibit the expression level of MMP2, which has been shown to be responsible for the migration and invasion of many kinds of tumors. This is the first study to establish a possible causal relationship between LGR4 and expression of MMP2.…”

Section: Discussionmentioning

confidence: 73%

The Interplay of MicroRNA-34a, LGR4, EMT-Associated Factors, and MMP2 in Regulating Uveal Melanoma Cells

Hou

Han

Yang

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. MicroRNA-34a (miR-34a) has been implicated in many biological processes. It is downregulated in uveal melanoma, and introduction of miR-34a inhibits the proliferation and migration of uveal melanoma cells. Leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) is a novel target of miR-34a identified first in retinal pigment epithelial cells. In this study, we sought to evaluate the interaction of miR-34a and LGR4 in uveal melanoma and its downstream mechanisms. METHODS. The expression of LGR4, epithelial-mesenchymal transition (EMT)-associated factors, and matrix metalloproteinase 2 (MMP2) in uveal melanoma cells was assessed by immunoblotting and immunofluorescence analysis. MicroRNA-34a mimic molecules, LGR4 small interfering RNA (siRNA), or MMP2-specific siRNA were transiently transfected into uveal melanoma cells. In vitro scratch and Transwell assays were used to evaluate the migratory and invasive potential of the resultant uveal melanoma cells. RESULTS. LGR4 is upregulated in uveal melanoma cells. Introduction of miR-34a significantly decreased the expression level of LGR4. Transfection with miR-34a or knockdown of LGR4 attenuated the aggressiveness of uveal melanoma cells. In addition, there was a decrease in the expression of mesenchymal markers N-cadherin, vimentin, and Snail following miR-34a introduction or knockdown of LGR4. Finally, MMP2 was found to be a downstream effector for miR-34a and LGR4 that regulates the migration and invasion of uveal melanoma cells. CONCLUSIONS. MicroRNA-34a negatively controls LGR4, thereby inhibiting the migration and invasion of uveal melanoma cells. Ultimately, both miR-34a and LGR4 impact the aggressiveness of uveal melanoma with alterations in the markers of the EMT. MMP2 is a downstream effector that influences the metastasis seen with uveal melanoma cells.

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Tumor suppressor microRNA-34a inhibits cell migration and invasion by targeting MMP-2/MMP-9/FNDC3B in esophageal squamous cell carcinoma

Cited by 55 publications

References 59 publications

Long non-coding RNA PART1 promotes intervertebral disc degeneration through regulating the�miR‑93/MMP2 pathway in nucleus pulposus cells

Long non-coding RNA PART1 promotes intervertebral disc degeneration through regulating the�miR‑93/MMP2 pathway in nucleus pulposus cells

The NOTCH1-HEY1 pathway regulates self-renewal and epithelial-mesenchymal transition of salivary adenoid cystic carcinoma cells

The Interplay of MicroRNA-34a, LGR4, EMT-Associated Factors, and MMP2 in Regulating Uveal Melanoma Cells

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