Dataset Information

MiR-107 inhibited malignant biological behavior of non-small cell lung cancer cells by regulating the STK33/ERK signaling pathway in vivo and vitro.

ABSTRACT:

Background

The role of miRNAs in non-small cell lung cancer (NSCLC) has been broadly studied and confirmed, and miR-107 has attracted an ever-growing level of attention. This study set out to research the mechanism of the effect of miR-107 on the malignant biological behavior of NSCLC in vivo and vitro.

Methods

The expression of miRNAs related to the development of NSCLC was detected by RT-qPCR. Western blotting was carried out to detect expression levels of serine/threonine kinase 33 (STK33) and proteins related to the extracellular regulated protein kinases (ERK) signaling pathway, while cell proliferation was detected using cell counting kit-8 (CCK-8). The cell apoptosis rate was measured using flow cytometry. The invasion ability was detected by Transwell assay. In vivo tumor growth assays were performed on mice. The expression ERK signaling pathway-related proteins in vivo was evaluated by immunohistochemistry staining. The targeted relationship between miR-107 and STK33 was confirmed by the dual luciferase reporter gene.

Results

In NSCLC cell lines and tissues, miR-107 was downregulated. Overexpression of miR-107 inhibited malignant biological behavior of NSCLC cell lines, and suppressed tumor growth in vivo. In addition, STK33 is one of the target genes of miR-107. Therefore, miR-107 suppressed cell proliferation and invasion and promoted tumor growth in vivo and cell apoptosis of NSCLC in vitro. The mechanism was found to be miR-107 targeting STK33, and a lack of STK33 led to the activation of ERK signaling pathway.

Conclusions

miR-107 inhibited malignant biological behavior of NSCLC through regulation of the STK33/ERK signaling pathway.

SUBMITTER: Wei X

PROVIDER: S-EPMC7212150 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

miR-107 inhibited malignant biological behavior of non-small cell lung cancer cells by regulating the STK33/ERK signaling pathway <i>in vivo</i> and <i>vitro</i>.

Wei Xueqiang X Lei Yujie Y Li Minjie M Zhao Guangqiang G Zhou Yongchun Y Ye Lianhua L Huang Yunchao Y

Journal of thoracic disease 20200401 4

<h4>Background</h4>The role of miRNAs in non-small cell lung cancer (NSCLC) has been broadly studied and confirmed, and miR-107 has attracted an ever-growing level of attention. This study set out to research the mechanism of the effect of miR-107 on the malignant biological behavior of NSCLC <i>in vivo</i> and <i>vitro</i>.<h4>Methods</h4>The expression of miRNAs related to the development of NSCLC was detected by RT-qPCR. Western blotting was carried out to detect expression levels of serine/t ...[more]

PMID: 32395291

Similar Datasets

Project description:BackgroundThe diagnostic utility of SRY-box transcription factor 10 (SOX10) expression in basal-like breast cancer (BLBC) has been reported previously. However, the effect of SOX10 on the malignancy of BLBC cells and the underlying molecular mechanisms remain unelucidated. Here, we investigate the regulatory mechanisms and roles of SOX10 in BLBC progression.MethodsSequencing data from patients with BLBC were extracted from the Cancer Genome Atlas database to determine the transcriptomic levels of SOX10 across breast cancer subtypes. Subsequently, the bioinformatics relevance of SOX10 in BLBC was investigated. Immunohistochemical assays were used to corroborate the protein expression of SOX10 in clinicopathological specimens (human breast cancer paraffin tissues). RNA interference was used to downregulate SOX10 expression, and the efficiency of interference was evaluated using quantitative PCR. The expression levels of molecules related to the epithelial-mesenchymal transition (EMT) pathway were determined by western blotting. Various assays, such as transwell, colony formation, and flow apoptosis assays, were conducted to assess the malignancy of BLBC cells (MDA-MB-231).ResultsBioinformatics analyses revealed the differential expression of SOX10 in various breast cancer subtypes. An association between SOX10 and immune checkpoint expression was observed in BLBC. Additionally, immune correlation analysis indicated a positive relationship between SOX10 expression and effector immune cells. SOX10 was identified as a potential immunotherapeutic target. Juxtaposed with non-basal-like breast cancer (N-BLBC) and breast adenosis, immunohistochemical analysis revealed the upregulated expression of SOX10 in BLBC, indicating its potential diagnostic significance. Single-gene functional enrichment analysis indicated that SOX10 is associated with EMT and the tumor inflammatory index. Experimental outcomes from cellular assays suggested that the downregulation of SOX10 inhibited multiple malignancy-associated behaviors in MDA-MB-231 cells, specifically affecting the EMT process, migration, invasion, proliferation, clone formation, and anti-apoptotic activities.ConclusionsWe concluded that SOX10 contributes to the malignancy of BLBC cells by modulating the EMT pathway. Moreover, we observed a notable correlation between SOX10 expression and immune responses, indicating the potential significance of SOX10 in immunotherapy.

Project description:Colorectal carcinoma (CRC) is a common malignant tumor of the digestive tract. It is characterized by a high degree of malignancy, early metastasis and poor prognosis. Studies have shown the effect of miR-369-3p on the biological function of a variety of tumors. However, the mechanism by which miR-369-3p and its potential target genes participate in the pathogenesis of CRC has not been elucidated. This study aims to study the relationship between miR-369-3p and transcription factor 4 (TCF4), to reveal the mechanism of the occurrence and development of CRC, and to provide a promising target for the treatment of CRC. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the miR-369-3p levels in CRC tissues and cells. miR-369-3p mimics and/or TCF4 overexpression vectors were transfected into SW480 cells. The expression of miR-369-3p and TCF4 mRNA was detected using RT-qPCR. Bioinformatics analysis predicted the binding site of miR-369-3p to the TCF4 3'UTR, and the targeting relationship was verified by a dual luciferase reporter gene assay. Cell proliferation and invasion were investigated by labeled immunofluorescence assay using BrdU antibody and Transwell assay. The oxidative stress ability of cells was determined by commercial kits. The levels of proteins related to cell proliferation and invasion were measured by western blotting. The level of miR-369-3p was significantly down-regulated in CRC tissues and cell lines, especially in SW480 cells (P<0.05). The expression of TCF4 was negatively correlated with that of miR-369-3p. High levels of miR-369-3p targeting TCF4 suppressed cell proliferation and downregulated the protein expression of Ki67 and PCNA (P<0.05). Overexpressed miR-369-3p binding TCF4 inhibited cell invasion and decreased the protein levels of vascular endothelial growth factor (VEGF) and E-cadherin (P<0.05). Furthermore, upregulation of miR-369-3p increased the activity of superoxide dismutase (SOD) while decreasing the content of malondialdehyde (MDA) and activity of lactate dehydrogenase (LDH) by blocking the expression of TCF4 (P<0.05). MiR-369-3p inhibits the proliferation, invasion and oxidative stress of CRC cells by targeting TCF4, thus defining miR-369-3p as a potential target for the diagnosis and treatment of CRC.

Project description:Objective Acute lung injury (ALI) increases sepsis morbidity and mortality. LncRNA H19 plays a critical role in sepsis. miR-107 is highly-expressed and TGFβ type III receptor (TGFBR3) is poorly-expressed in sepsis, yet their roles in sepsis development require further investigation. This study aimed to investigate the mechanism of H19 in alleviating sepsis-induced ALI through the miR-107/TGFBR3 axis. Methods Mice were intravenously injected with Ad-H19 adenovirus vector or control vector one week before establishing the mouse model of cecal ligation and puncture (CLP). Pulmonary microvascular endothelial cells (PMVECs) were transfected with oe-H19 or oe-NC plasmids and then stimulated by lipopolysaccharide (LPS). Lung injury was assessed via hematoxylin–eosin staining, measurement of wet-to-dry (W/D) ratio, and TUNEL staining. Levels of H19, miR-107, and TGFBR3 were determined by RT-qPCR. Apoptosis of PMVECs was evaluated by flow cytometry. Levels of Bax and Bcl-2 in lung tissues and PMVECs were measured using Western blot. Total protein concentration and the number of total cells, neutrophils, and macrophages in bronchoalveolar lavage fluid (BALF) were quantified. Levels of TNF-α, IL-1β, IL-6, and IL-10 in BALF, lung tissues, and PMVECs were measured by ELISA. Cross-linking relationships among H19, miR-107 and TGFBR3 were verified by dual-luciferase and RIP assays. Results H19 was poorly-expressed in CLP-operated mice. H19 overexpression attenuated sepsis-induced ALI, which was manifested with complete alveolar structure, decreased lung injury score and lung W/D ratio, and inhibited apoptosis in CLP-operated mice, which was manifested with decreased number of TUNEL-positive cells and Bax level and increased Bcl-2 level. CLP-operated mice had increased concentration of total protein and number of total cells, neutrophils, and macrophages in BALF, which was nullified by H19 overexpression. H19 overexpression declined levels of TNF-α, IL-1β, and IL-6 and elevated IL-10 levels. H19 inhibited LPS-induced PMVEC apoptosis and pro-inflammatory cytokine production. H19 targeted TGFBR3 as the ceRNA of miR-107. miR-107 overexpression or silencing TGFBR3 partially averted the inhibition of H19 overexpression on LPS-induced PMVEC apoptosis and pro-inflammatory cytokine production. Conclusion LncRNA H19 inhibited LPS-induced PMVEC apoptosis and pro-inflammatory cytokine production and attenuated sepsis-induced ALI by targeting TGFBR3 as the ceRNA of miR-107. Supplementary Information The online version contains supplementary material available at 10.1186/s12890-022-02091-y.