miR-29b negatively regulates MMP2 to impact gastric cancer development by suppress gastric cancer cell migration and tumor growth

Wang, Tao; Hou, Jingjing; Jian, Shuo; Luo, Qin; Jie, Wei; Wang, Xuegang; Bai, Peide; Duan, Bo; Xing, Jinchun; Cai, Jun

doi:10.7150/jca.26263

Cited by 36 publications

(28 citation statements)

References 37 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: 56%

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: 56%

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 effects of these coding genes on CRC prognosis were comprehensively analyzed, and a prognostic model of CRC was constructed with six mRNA signatures (COL1A1, COL1A2, COL3A1, COL4A3, COL4A6 and MMP2). Among them, COL1A1, COL1A2, COL3A1 and MMP2 have been reported to serve vital roles in tumor invasion, and are thus associated with poor prognosis (54)(55)(56)(57). COL4A3 and COL4A6, encoding COL IV alpha chains 3 and 6, respectively, are required for correct basement membrane (BM) formation, and mutations within these genes affect BM stability (58,59).…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of abnormal matrix collagen remodeling in colorectal cancer based on histologic and bioinformatics analysis

Liang

Huang

et al. 2020

Oncol Rep

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As the major component of the tumor matrix, collagen greatly influences tumor invasion and prognosis. The present study compared the remodeling of collagen and collagenase in 56 patients with colorectal cancer (CRC) using Sirius red stain and immunohistochemistry, exploring the relationship between collagen remodeling and the prognosis of CRC. Weak or strong changes in collagen fiber arrangement in birefringence were observed. With the exception of a higher density, weak changes equated to a similar arrangement in normal collagen, while strong changes facilitated cross-linking into bundles. Compared with normal tissues, collagen I (COL I) and III (COL III) deposition was significantly increased in CRC tissues, and was positively correlated with the metastasis status. In tissues without distant metastasis, collagen IV (COL IV) levels were higher than that in normal tissues, while in tissues with distant metastasis, collagen IV expression was significantly lower. Furthermore, the expression of matrix metalloproteinase (MMP)-1, MMP-2, MMP-7, MMP-9 and lysyl oxidase-like 2 (LOXL2) was found to be elevated in the cancer stroma, which contributed to the hyperactive remodeling of collagen. The association between collagen-related genes and the occurrence and prognosis of CRC were analyzed using biometric databases. The results indicated that patients with upregulated expression of a combination of coding genes for collagen and collagenase exhibited poorer overall survival times. The coding genes COL1A1-2, COL3A1, COL4A3, COL4A6 and MMP2 may therefore be used as biomarkers to predict the prognosis of patients with CRC. Furthermore, the results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggest that collagen may promote tumor development by activating platelets. Collectively, the abnormal collagen remodeling, including associated protein and coding genes is associated with the tumorigenesis and metastasis, affecting the prognosis of patients with CRC.

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“…Additionally, alterations in MMPs expression and activity occur in tumor biology processes [48]. Recent study shows that miR-29b negatively regulates MMP2 expression and activity to suppress gastric cancer cell migration and tumor growth [49]. In addition, lncRNA PVT1 promotes angiogenesis via STAT3/VEGFA axis in gastric cancer [50].…”

Section: Discussionmentioning

confidence: 99%

SRSF10 inhibits biogenesis of circ-ATXN1 to regulate glioma angiogenesis via miR-526b-3p/MMP2 pathway

Liu

Shen

Zhu

et al. 2020

J Exp Clin Cancer Res

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Background: Angiogenesis plays an important role in the progress of glioma. RNA-binding proteins (RBPs) and circular RNAs (circRNAs), dysregulated in various tumors, have been verified to mediate diverse biological behaviors including angiogenesis. Methods: Quantitative real-time PCR (qRT-PCR) and western blot were performed to detect the expression of SRSF10, circ-ATXN1, miR-526b-3p, and MMP2/VEGFA. The potential function of SRSF10/circ-ATXN1/miR-526b-3p axis in glioma-associated endothelial cells (GECs) angiogenesis was further studied. Results: SRSF10 and circ-ATXN1 were significantly upregulated in GECs compared with astrocyte-associated endothelial cells (AECs). Knockdown of SRSF10 or circ-ATXN1 significantly inhibited cell viability, migration and tube formation of GECs where knockdown of SRSF10 exerted its function by inhibiting the formation of circ-ATXN1. Moreover, the combined knockdown of SRSF10 and circ-ATXN1 significantly enhanced the inhibitory effects on cell viability, migration and tube formation of GECs, compared with knockdown of SRSF10 and circ-ATXN1, respectively. MiR-526b-3p was downregulated in GECs. Circ-ATXN1 functionally targeted miR-526b-3p in an RNA-induced silencing complex. Up-regulation of miR-526b-3p inhibited cell viability, migration and tube formation of GECs. Furthermore, miR-526b-3p affected the angiogenesis of GECs via negatively regulating the expression of MMP2/ VEGFA. Conclusion: SRSF10/circ-ATXN1/miR-526b-3p axis played a crucial role in regulating the angiogenesis of GECs. The above findings provided new targets for anti-angiogenic therapy in glioma.

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miR-29b negatively regulates MMP2 to impact gastric cancer development by suppress gastric cancer cell migration and tumor growth

Cited by 36 publications

References 37 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

Prognostic significance of abnormal matrix collagen remodeling in colorectal cancer based on histologic and bioinformatics analysis

SRSF10 inhibits biogenesis of circ-ATXN1 to regulate glioma angiogenesis via miR-526b-3p/MMP2 pathway

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