Long non-coding RNA ZEB2-AS1 promotes the proliferation, metastasis and epithelial mesenchymal transition in triple-negative breast cancer by epigenetically activating ZEB2.

The triple-negative breast cancer is the most malignant type of breast cancer. Its pathogenesis and prognosis remain poor despite the significant advances in breast cancer diagnosis and therapy. Meanwhile, long noncoding RNAs (LncRNAs) play a pivotal role in the progression of malignant tumors. In this study, we found that LncRNA-ZEB2-AS1 was dramatically up-regulated in our breast cancer specimens and cells (MDA231), especially in metastatic tumor specimens and highly invasive cells, and high lncRNA-ZEB2-AS1 expression is associated with clinicopathologic features and short survival of breast cancer patients. LncRNA-ZEB2-AS1 promotes the proliferation and metastasis of MDA231 cells in SCID mice. Thus, it is regarded as an oncogene in triple-negative breast cancer. It is mainly endo-nuclear and situated near ZEB2, positively regulating ZEB2 expression and activating the epithelial mesenchymal transition via the PI3K/Akt/GSK3ß/Zeb2 signaling pathway. Meanwhile, EGF-induced F-actin polymerization in MDA231 cells can be suppressed by reducing lncRNA-ZEB2-AS1 expression. The migration and invasion of triple-negative breast cancer can be altered through cytoskeleton rearrangement. In summary, we demonstrated that lncRNA-ZEB2-AS1 is an important factor affecting the development of triple-negative breast cancer and thus a potential oncogene target.

Dock1 promotes the mesenchymal transition of glioma and is modulated by MiR-31.

AIMS: This research aimed to examine the relationship between Dock1 and miR-31 and to determine the effect of miR-31 on the mesenchymal transition and invasiveness of glioma. METHODS: Real-time PCR was used to measure the expression of miR-31 and other RNAs. The transfection was used to manipulate the expression levels of Dock1 and miR-31 in cancer cells. Western blot was used to detect the expression of Dock1 and other related proteins. Wound healing, Matrigel invasion and chemotaxis assays were performed to detect the invasion and migration of glioma cell lines. The actual binding site of miR-31 to the 3'-untranslated region of Dock1 was confirmed through luciferase assay and RNA immunoprecipitation. Methylation-specific PCR was performed to detect the methylation level of miR-31 in both glioma cell lines and tissues. RESULTS: Dock1 can promote the IL8-induced chemotaxis and mesenchymal transition of glioma cells through the NF-κB/Snail signalling pathway. The protein levels of Dock1 in glioma cell lines and clinical specimens were negatively correlated with miR-31 expression, and Dock1 was directly targeted by miR-31. Animal experiments showed that Dock1 downregulation and miR-31 overexpression reduced glioma cell invasion. Investigation of the underlying molecular mechanism revealed that miR-31 downregulation was attributable to the hypermethylation of the promoter region of miR-31 in glioma cells. CONCLUSION: Dock1 modulation by miR-31 plays an important function in glioma invasion both in vitro and in vivo. This study provides new insights into the invasion of glioma cells and might therefore contribute to the development of new antiglioma strategies.

Erratum to: RAGE-binding S100A8/A9 promotes the migration and invasion of human breast cancer cells through actin polymerization and epithelial-mesenchymal transition.

Erratum to: Breast Cancer Res Treat (2013),142:297­309,DOI 10.1007/s10549-013-2737-1.In the original publication, the images in Fig. 3 were mistakenly selected from other experiments in which similar procedures were performed. The corrected Fig. 3 is given in this erratum.

Linc00707 regulates autophagy and promotes the progression of triple negative breast cancer by activation of PI3K/AKT/mTOR pathway.

Triple-negative breast cancer (TNBC) is a pathological subtype of breast cancer (BC) with high malignancy, strong invasiveness and poor prognosis. Long non-coding RNA (LncRNA) plays an important role during tumorigenesis. We identified that Linc00707 was upregulated in TNBC tissues by TCGA database and RT-qPCR assay, compared with normal breast tissues and other subtypes of BC. Linc00707 promoted TNBC cells proliferation, migration and invasion. Furthermore, we found that knockdown of Linc00707 influenced autophagy via PI3K/AKT/mTOR signaling pathway in TNBC cells. Linc00707 affected the progress of TNBC cells through affecting autophagy. Further mechanistic experiments confirmed that Linc00707 could competitively bind with miR-423-5p to up-regulate MARCH2 expression, ultimately promoting TNBC progression and autophagy through PI3K/AKT/mTOR pathway. In conclusion, we demonstrate that Linc00707 is a key molecule in tumor progression and may be an effective target for patients with TNBC.

Development and validation of a predictive model for double-J stent encrustation after upper urinary tract calculi surgery.

The study is aimed to establish a predictive model of double-J stent encrustation after upper urinary tract calculi surgery. We collected the clinical data of 561 patients with indwelling double-J tubes admitted to a hospital in Shandong Province from January 2019 to December 2020 as the modeling group and 241 cases of indwelling double-J tubes from January 2021 to January 2022 as the verification group. Univariate and binary logistic regression analyses were used to explore risk factors, the risk prediction equation was established, and the receiver operating characteristic (ROC) curve analysis model was used for prediction. In this study, 104 of the 561 patients developed double-J stent encrustation, with an incidence rate of 18.5%. We finally screened out BMI (body mass index) > 23.9 (OR = 1.648), preoperative urine routine white blood cell quantification (OR = 1.149), double-J tube insertion time (OR = 1.566), postoperative water consumption did not reach 2000 ml/d (OR = 8.514), a total of four factors build a risk prediction model. From the ROC curve analysis, the area under the curve (AUC) was 0.844, and the maximum Oden index was 0.579. At this time, the sensitivity was 0.735 and the specificity was 0.844. The research established in this study has a high predictive value for the occurrence of double-J stent encrustation in the double-J tube after upper urinary tract stone surgery, which provides a basis for the prevention and treatment of double-J stent encrustation.

PTTG1 promotes migration and invasion of human non-small cell lung cancer cells and is modulated by miR-186.

Deeper mechanistic understanding of non-small cell lung cancer (NSCLC), a leading cause of total cancer-related deaths, may facilitate the establishment of more effective therapeutic strategies. In this study, pituitary tumor transforming gene (PTTG1) expression was associated with lymph node and distant metastasis in patients with NSCLC and was correlated with patient survival. Reduction of PTTG1 by small interfering RNA (siRNA) inhibits the migration and invasion of NSCLC cells by mediating matrix metalloproteinases expression. To the best of our knowledge, this study is the first to report that PTTG1 promotes epidermal growth factor (EGF) induced the phosphorylation of LIN-11, Isl1 and MEC-3 protein domain kinase and cofilin, a critical step in cofilin recycling and actin polymerization. Additionally, EGF-induced Akt phosphorylation was suppressed through knockdown of PTTG1. Interestingly, miR-186 can modulate PTTG1 protein expression. As observed from the animal experiment in this study, knockdown of PTTG1 through siRNA and overexpression of miR-186 inhibited invasive activity of NSCLC cells toward the SCID mice lung. In summary, our in vitro and in vivo results indicate that PTTG1 modulated by miR-186 has an important function in NSCLC invasion/metastasis. This study identified both PTTG1 and miR-186 as potential anti-invasion targets for therapeutic intervention in NSCLC.

RAGE-binding S100A8/A9 promotes the migration and invasion of human breast cancer cells through actin polymerization and epithelial-mesenchymal transition.

S100A8/A9 proteins are members of EF-hand calcium-binding proteins secreted by neutrophils and activated monocytes. S100A8/A9 has cell growth-promoting activity at low concentrations by binding to the receptor for advanced glycation end products (RAGE). In this study, we report for the first time that S100A8/A9 promoted the invasion of breast cancer cells depending on RAGE. In addition, RAGE binding to S100A8/A9 promoted the phosphorylation of LIN-11, Isl1, and MEC-3 protein domain kinase, as well as cofilin. This phosphorylation is a critical step in cofilin recycling and actin polymerization. Interestingly, RAGE binding to S100A8/A9 enhanced cell mesenchymal properties and induced epithelial-mesenchymal transition. Mechanistically, RAGE binding to S100A8/A9 stabilized Snail through the NF-κB signaling pathway. Based on these observations, RAGE expression in breast cancer cells was associated with lymph node and distant metastases in patients with invasive ductal carcinoma. Moreover, RAGE binding to S100A8/A9 promoted lung metastasis in vivo. In summary, our in vitro and in vivo results indicated that RAGE binding to S100A8/A9 played an important role in breast cancer invasion/metastasis. This study identified both RAGE and S100A8/A9 as potential anti-invasion targets for therapeutic intervention in breast cancer.

[Mechanism of miR-186-5p Regulating PRKAA2 to Promote Ferroptosis 
in Lung Adenocarcinoma Cells].

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common type of non-small cell lung cancer, and any change of miRNAs expression will affect the degree of target regulation, thus affecting intracellular homeostasis. This study verified that miR-186-5p could inhibit the proliferation, migration and invasion of LUAD cells by regulating PRKAA2. METHODS: Previous investigations found that the expression of miR-186-5p was markedly suppressed in LUAD. Bioinformatics method is used to predict the target protein related to ferroptosis downstream and inquire about its expression level in LUAD and its influence on the survival of patients. Double luciferase verified the binding site of PRKAA2 and miR-186-5p. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the expression of PRKAA2. The effects of miR-186-5p of LUAD cells as well as the mechanism by which miR-186-5p inhibits Fer-1's sensitivity to ferroptosis were confirmed by EdU, Transwell, and scratch assays. The effect of miR-186-5p on the amount of reactive oxygen species (ROS) in LUAD cells was discovered using ROS experiment. Malondialdehyde (MDA) and glutathione (GSH) experiments were used to detect the effects of miR-186-5p and PRKAA2 on ferroptosis index of LUAD cells. The concentration of lipid ROS (L-ROS) in LUAD cells were measured using the L-ROS tests to determine the effects of miR-186-5p and PRKAA2. RESULTS: The expression of PRKAA2 is up-regulated, and a high level of PRKAA2 expression was associated with a poor prognosis for patients with LUAD. Overexpression of miR-186-5p decreased the gene and protein expression of PRKAA2. By promoting ferroptosis, miR-186-5p overexpression prevented lung cancer cells from proliferating, invading, and migrating. ROS could be produced in higher amounts in LUAD cells due to miR-186-5p. Overexpression of miR-186-5p and knockdown PRKAA2 up-regulated MDA content and reduced GSH content in LUAD cells, respectively. miR-186-5p could increase the content of L-ROS and promote the ferroptosis sensitivity of LUAD cells by targeting PRKAA2. CONCLUSIONS: miR-186-5p promotes ferroptosis of LUAD cells through targeted regulation of PRKAA2, thus inhibiting the proliferation, invasion and migration of LUAD.
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[miR-30b-3p Inhibits the Proliferation and Invasion of Lung Adenocarcinoma 
by Targeting COX6B1].

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common clinical histological subtype of lung cancer and microRNAs (miRNAs) are a type of small non-coding RNAs which play a central role in cells. miR-30b-3p plays a key effect in many types of carcinoma, but there is still very little research on how it works in lung adenocarcinoma. The role and mechanism of miR-30b-3p in the proliferation and invasion of LUAD were explored in this study, to provide new targets for inhibiting the proliferation and invasion of LUAD. METHODS: NCBI database was used to screen out miRNA with obvious differential expression, and the differential expression and survival curve were searched by StarBase database. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the relative expression of miR-30b-3p in each lung adenocarcinoma cell line. 5-ethynyl-2'-deoxyuridine (EdU) cell proliferation assay and Transwell invasion assay were used to detect the proliferation and invasion of A549 cells in each group. The target genes of miR-30b-3p were determined by the target gene prediction websites. Western blot assay was used to detect the expression of COX6B1 in each group of A549 cells. Double luciferase assay was used to verify the targeted binding relationship between miR-30b-3p and COX6B1. RESULTS: The expression of miR-30b-3p in lung adenocarcinoma tissues and lung adenocarcinoma cells was downregulated (P<0.05). Low expression levels of miR-30b-3p were associated with poor prognosis in patients with lung adenocarcinoma (P=0.005,8). Overexpression of miR-30b-3p could inhibit the proliferation and the invasion of lung adenocarcinoma cells (P<0.05). Double luciferase assay proved that miR-30b-3p could target and bind to COX6B1 (P<0.05). Western blot analysis showed that the overexpression of miR-30b-3p could downregulate the expression of COX6B1 in A549 cells (P<0.05). EdU cell proliferation assay and Transwell invasion assay showed that the overexpression of miR-30b-3p could reverse the promoting effect of upregulation of COX6B1 on proliferation and invasion in lung adenocarcinoma cells (P<0.05). CONCLUSIONS: miR-30b-3p acts as a tumor suppressor gene in lung adenocarcinoma, and it can inhibit the proliferation and invasion of lung adenocarcinoma by targeting the expression of COX6B1.

MiR-379-5p inhibits the proliferation, migration, and invasion of breast cancer by targeting KIF4A.

BACKGROUND: Many studies have shown that microRNAs (miRNAs) play an essential role in gene regulation and tumor development. This study aimed to explore the expression of miR-379-5p and its mechanisms of affecting proliferation, migration, and invasion in breast cancer (BC). METHODS: MiRNAs and mRNAs expression data of BC and normal breast tissue samples were downloaded from the TCGA and GEO databases. qRT-PCR was used to detect the expression of miR-379-5p in human normal breast epithelial cell lines and human BC cell lines. The proliferation ability of transfected cells was detected by colony formation and EdU assays. The mobility and invasion ability of transfected cells was measured by wound healing and transwell assays. The relative protein expression of transfected cells was detected by western blot. Dual luciferase reporter assay was performed to identify the targeted binding of miR-379-5p and KIF4A. RESULTS: MiR-379-5p was lowly expressed in BC tissue samples and BC cell lines. The target genes of miR-379-5p were involved in many cancer-related signaling pathways. PPI analysis and the cytoHubba algorithm of Cytoscape identified 10 genes as the hub genes. Survival analysis showed that only KIF4A expression in 10 hub genes was significantly associated with the prognosis of BC patients and was significantly upregulated in BC. Overexpression of miR-379-5p inhibited proliferation, migration, and invasion in the BC cell line MDA-MB-231, which could be reversed by KIF4A. CONCLUSIONS: MiR-379-5p inhibits proliferation, migration, and invasion of BC by targeting KIF4A.

[Research Progress of Pharmacological Therapy and Nutritional Support for Cachexia 
in Lung Cancer Patients].

Cachexia is a common complication in patients with lung cancer. It aggravates the toxic and side effects of chemotherapy, hinders the treatment plan, weakens the responsiveness of chemotherapy, reduces the quality of life, increases complications and mortality, and seriously endangers the physical and mental health of patients with lung cancer. The causes and pathogenesis of tumor cachexia are extremely complex, which makes its treatment difficult and complex. Controlling cachexia in lung cancer patients requires many means such as anti-tumor therapy, inhibition of inflammatory response, nutritional support, physical exercise, and relief of symptoms to exert the synergistic effect of multimodal therapy against multiple mechanisms of tumor cachexia. To date, there has been a consensus within the discipline that no single therapy can control the development of cachexia. Some therapies have made some progress, but they need to be implemented in combination with multimodal therapy after fully assessing the individual characteristics of lung cancer patients. This article reviews the application of drug therapy and nutritional support in lung cancer patients, and looks forward to the research direction of cachexia control in lung cancer patients.
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LncRNA-AC009948.5 promotes invasion and metastasis of lung adenocarcinoma by binding to miR-186-5p.

Background: Long non-coding RNAs (LncRNAs) has been confirmed to play a crucial role in the development and progression of various cancer types. Here we evaluated the expression profiles of LncRNAs in Lung adenocarcinoma (LUAD) tissues and identified a novel LncRNA, termed LncRNA-AC009948.5. However, the role and potential molecular mechanisms of this novel LncRNA in LUAD carcinogenesis is unknown. Methods: Regarding the public databases and based on integrating bioinformatics analyses, we determined whether LncRNA-AC009948.5 exerts its oncogenic functions via sponging miR-186-5p in LUAD. Furthermore, we determined whether NCAPG2 was a downstream target of miR-186-5p. Moreover, the expression level and biological function of LncRNA-AC009948.5 in LUAD were determined by qRT-PCR, cell apoptosis, Edu, transwell, wound healing and western blot assays. Besides, xenograft mice were established for validation. We explored the expression of LncRNA-AC009948.5 and its roles in the prognosis of LUAD. Results: LncRNA expression microarray data indicate that LncRNA-AC009948.5 is upregulated in LUAD samples. The present study confirmed the upregulation of LncRNA-AC009948.5 in LUAD tissues and cells. Encreased expression of LncRNA-AC009948.5 was correlated with tumor size, lymph nodes, distant metastasis and histological grade, and poor prognosis.LncRNA-AC009948.5 knockdown significantly inhibited cell proliferation, migration, and invasion in vitro, as well as tumorigenesis and metastasis in vivo. Conversely, LncRNA-AC009948.5 upregulated had opposite effects. Mechanistically, we elucidated that LncRNA-AC009948.5 could directly bind to miR-186-5p and subsequently suppress expression of the target gene of NCAPG2. Conclusions: LncRNA-AC009948.5 promotes lung adenocarcinoma cells metastasis via the miR-186-5p/NCAPG2 axis and activation of the EMT process. Which may serve as potential targets for the treatment of LUAD in the future.

The miR-4732-5p/XPR1 axis suppresses the invasion, metastasis, and epithelial-mesenchymal transition of lung adenocarcinoma via the PI3K/Akt/GSK3ß/Snail pathway.

The roles of microRNAs (miRNAs) in the occurrence, metastasis, and prognosis of lung adenocarcinoma (LUAD) have been drawing extensive attention from researchers. The aim of this study is to identify the effects of miR-4732-5p on the migration, invasion, and metastasis of LUAD. In this study, we found that the expression of miR-4732-5p was decreased in LUAD based on the data derived from The Cancer Genome Atlas (TCGA) database, tissues, and cell lines. LUAD patients with a low expression of miR-4732-5p exhibited a lower survival rate. Meanwhile, miR-4732-5p could directly target xenotropic and polytropic retrovirus receptor 1 (XPR1), and elevated XPR1 was observed in LUAD mRNA microarrays, Gene Expression Omnibus (GEO), and The Human Protein Atlas (HPA) database. Overexpression of miR-4732-5p significantly inhibits the migration, invasion, and metastasis of LUAD in vitro and in vivo, which can be reversed by overexpression of XPR1. We also found that the PI3K/Akt/GSK3ß/Snail pathway induced by EGF induced EMT could be inhibited by miR-4732-5p overexpression and XPR1 knockdown. The migration and invasion of LUAD could be converted by cytoskeletal rearrangements, and the polymerization of EGF induced F-actin in A549 cells could be inhibited by elevated miR-4732-5p. Our results suggest that miR-4732-5p exerts anti-tumor effects on the invasion and metastasis of LUAD by regulating XPR1 in vivo and in vitro, indicating that the miR-4732-5p/XPR1 axis may be a potential target for LUAD therapeutic intervention.

[miR-144-3p Inhibits the Invasion and Metastasis of Lung Adenocarcinoma Cells 
by Targeting IRS1].

BACKGROUND: MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression, influence cellular processes, and promote disease development. Variations in miRNA expression have been observed in many diseases, including hepatitis, cardiovascular disease, and cancer. The aim of this study is to investigate the effect of miR-144-3p on the invasion and metastasis of lung adenocarcinoma by targeting recombinant insulin receptor substrate 1 (IRS1). METHODS: The expression of miR-144-3p in patients with lung adenocarcinoma was queried through bioinformatics database. MirTarPathway was used to analyze the KEGG enrichment pathway of miRNA. The expression and plasmid transfection efficiency of miR-144-3p in lung adenocarcinoma cell lines were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Transwell assay was used to detect the changes of cell invasion and migration ability in different groups. Bioinformatics determined the key genes (Hub genes) of miR-144-3p; Double luciferase target assay was used to detect the mutual binding of miR-144 and IRS1. Western blot assay was used to detect the expression of IRS1 in different cell lines and the expression of after overexpression of miR-144. RESULTS: The expression of miR-144-3p in lung adenocarcinoma tissues was decreased, qRT-PCR results indicated that the expression of miR-144-3p in lung adenocarcinoma cell A549 was significantly decreased (P<0.05), and the overexpressed plasmid was successfully transfected (P<0.05). Overexpression of miR-144 decreased the ability of cell migration and invasion (P<0.05). The expression of IRS1 was up-regulated in lung adenocarcinoma tissues. Survival analysis showed that patients with lung adenocarcinoma with high IRS1 expression had a poor prognosis (P<0.05). Double luciferase assay results showed that miR-144 could specifically identify 3'-UTR of IRS1 and inhibit reporter enzyme expression (P<0.05). Western blot indicated that the expression of IRS1 was increased in A549 cells (P<0.05). After overexpression of miR-144, the expression level of IRS1 protein was decreased (P<0.05). Transwell experiment proved that miR-144-3p could inhibit invasion and metastasis of lung adenocarcinoma cells by targeting IRS1 (P<0.05). CONCLUSIONS: MiR-144-3p inhibits the invasion and migration of A549 cells through targeted regulation of IRS1, thus playing an anticancer role in tumors.

Cancer-associated fibroblast-derived exosomal miR-18b promotes breast cancer invasion and metastasis by regulating TCEAL7.

Studies have shown that cancer-associated fibroblasts (CAFs) play an irreplaceable role in the occurrence and development of tumors. Therefore, exploring the action and mechanism of CAFs on tumor cells is particularly important. In this study, we compared the effects of CAFs-derived exosomes and normal fibroblasts (NFs)-derived exosomes on breast cancer cells migration and invasion. The results showed that exosomes from both CAFs and NFs could enter into breast cancer cells and CAFs-derived exosomes had a more enhancing effect on breast cancer cells migration and invasion than NFs-derived exosomes. Furthermore, microRNA (miR)-18b was upregulated in CAFs-derived exosomes, and CAFs-derived exosomes miR-18b can promote breast cancer cell migration and metastasis by specifically binding to the 3'UTR of Transcription Elongation Factor A Like 7 (TCEAL7). The miR-18b-TCEAL7 pathway promotes nuclear Snail ectopic activation by activating nuclear factor-kappa B (NF-κB), thereby inducing epithelial-mesenchymal transition (EMT) and promoting cell invasion and metastasis. Moreover, CAFs-derived exosomes miR-18b could promote mouse xenograft model tumor metastasis. Overall, our findings suggest that CAFs-derived exosomes miR-18b promote nuclear Snail ectopic by targeting TCEAL7 to activate the NF-κB pathway, thereby inducing EMT, invasion, and metastasis of breast cancer. Targeting CAFs-derived exosome miR-18b may be a potential treatment option to overcome breast cancer progression.

miR-193a-3p Promotes the Invasion, Migration, and Mesenchymal Transition in Glioma through Regulating BTRC.

BACKGROUND: The present study is aimed at exploring the specific expression of miR-193a-3p and the mechanism underlying miR-193a-3p-mediated mesenchymal transition (MT), invasion, and migration in glioma. METHODS: The gene expression profile datasets of GSE39486 and GSE25676 were downloaded from the National Center for Biotechnology (NCBI). Data regarding the expression of miR-193a-3p and survival curves were derived from Chinese Glioma Genome Atlas (CGGA). Online websites including miRWalk, DIANA, and starbase were employed to predict the target genes for miR-193a-3p. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed by the Omicsbean online software. Module analysis of the protein-protein interaction (PPI) networks was performed by the plug-in Molecular Complex Detection (MCODE), and the degrees of genes were calculated by CytoHubba plug-in of Cytoscape. Survival curves were based on the Gene Expression Profile Interaction Analysis (GEPIA). Transwell, wound healing, and Western blot experiments were performed to investigate the effects of miR-193a-3p and beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC) on the invasion, migration, and MT of glioma. RESULTS: miR-193a-3p was highly expressed in glioma tissues and significantly correlated with poor survival in patients with glioma. The target genes for miR-193a-3p were involved in many cancer-related signaling pathways. The PPI showed 11 genes with both high degrees and MCODE scores in the network. Survival analysis demonstrated that the expression of BTRC was significantly correlated with the prognosis of patients with glioma. The results from the transwell, wound healing, and Western blot analyses suggested that miR-193a-3p promoted the invasion, migration, and MT of glioma cells, which could be reversed by BTRC. CONCLUSIONS: miR-193a-3p was upregulated in patients with glioma and could affect the invasion, migration, and MT of glioma by regulating BTRC.

MiR-429 suppresses proliferation and invasion of breast cancer via inhibiting the Wnt/ß-catenin signaling pathway.

BACKGROUND: microRNAs (miRNAs) have been verified as molecular targets for regulating tumor proliferation, invasion, and metastasis in tumor progression. However, the relationship between miRNAs and cellular energy metabolism in breast cancer still needs to be clarified. This study aimed to investigate the role of miR-429 in breast cancer progression. METHODS: Bioinformatic analyses were employed to detect the relationship between miR-429 and cancer-related signaling pathways. We used a Kaplan-Meier curve to analyze survival rate in patients with high or low expression of miR-429. We used real-time quantitative PCR (RT-qPCR) to detect the expression of miR-429 in different cell lines. Sh-con, over-miR-429, miR-429 inhibitor, and sh-inhibitor control were transfected. Colony formation and EDU assay were used to detect the proliferation of transfected cells. Wound healing and transwell assays were performed to detect the mobility and invasion ability of transfected cells. Western blot assay was used to detect relative protein expression in transfected cells and different tissues. Bioinformatic analyses were conducted to detect the target proteins expression in different breast cancer databases. Dual luciferase reporter assay was used to confirm the binding site between miR-429 and fibronectin 1 (FN1). RESULTS: The results of our study indicate that MiR-429 and its target genes are associated with cancer-related signaling pathways and that higher miR-429 expression corresponds with a better prognosis. When miR-429 was overexpressed, the proliferation, invasion of MDA-MB-231 were inhibited. MiR-429 was able to suppress the Wnt/ß-catenin signaling pathway, and FN1 overexpression could rescue the influence of over-miR-429. CONCLUSIONS: The results of our study suggest that miR-429 suppresses the proliferation and invasion of breast cancer via inhibiting the Wnt/ß-catenin signaling pathway.

[Mechanism of DERL3 Affecting the Proliferation, Invasion and Metastasis of Lung Adenocarcinoma A549 Cells].

BACKGROUND: Derlin 3 (DERL3) is downregulated in colorectal cancer (CRC) samples. Its level is closely linked to lymphatic metastasis or distant metastasis rate in CRC patients. However, its biological behavior in lung adenocarcinoma were rarely reported. The aim of this study is to investigate the ectopic expression of DERL3 in lung adenocarcinoma tissues and its effect on the invasion and metastasis of lung adenocarcinoma A549 cell line to reveal the possible mechanism of invasion and metastasis of lung adenocarcinoma. METHODS: Lung adenocarcinoma microarray gene chip data included 3 cases of lymph node metastasis and 3 cases of lung adenocarcinoma tissue without lymph node metastasis. The GEDS and Kaplan-Meier plot queries the survival curve and expression level of DERL3. Western blot was used to detect the expression of DERL3 in lung adenocarcinoma cells. The efficiency of knockdown DERL3 gene was detected by Western blot assay. Transwell detected the number of cells passing through the basement membrane of the transwell. EDU assay detected cell proliferation ability. Western blot detected the expression of epithelial-mesenchymal transition related proteins E-cadherin and Vimentin. RESULTS: The microarray gene chip results showed that compared with lung adenocarcinoma tissues without lymph node metastasis, 1,314 mRNAs in lung adenocarcinoma tissues with lymph node metastasis were up-regulated, 400 mRNAs were down (P<0.05). The expression of DERL3 increased in lung adenocarcinoma (P<0.05). The results of survival curve showed that the lung cancer patients with high expression of DERL3 with poor prognosis (P<0.05). Western blot results indicated that plasmid transfection was successful. Knockdown of DERL3 suppressed the ability of proliferation, invasion and migration in A549 cells (P<0.05). After knockdown of DERL3, the expression level of Vimentin was decreased, while E-cadherin expression increased (P<0.05). CONCLUSIONS: Knockdown of DERL3 inhibited the proliferation, invasion and metastasis of A549 cells.

[miR-93-5p promotes invasion and migration of triple negative breast cancer cells by targeting FGD5].

Objective To investigate the molecular mechanism by which miR-93-5p promotes the invasion and migration of triple negative breast cancer (TNBC) cells. Methods The miR-93-5p and faciogenital dysplasia-5 (FGD5) were screened out by Gene Expression Omnibus (GEO). Bioinformatics software was used to predict the candidate target genes for miR-93-5p. The relative expression of miR-93-5p in cells was detected by real-time quantitative PCR. Western blot was used to detect the relative expression of FGD5. TranswellTM assay was performed to detect the effects of miR-93-5p on the invasion and migration of MDA-MB-231 cells. The expression of FGD5 and survival curve in breast cancer and the correlation between miR-93-5p and FGD5 were analyzed by bioinformatics database. Dual luciferase reporter gene experiment was employed to verify the targeting relationship between miR-93-5p and FGD5. Results The miR-93-5p was highly expressed in TNBC tissues and cell lines. The higher the expression of miR-93-5p was, the worse the prognosis of breast cancer patients were. Knockdown of miR-93-5p inhibited the invasion and migration ability of MDA-MB-231 cells. Bioinformatics analysis showed that there were complementary sequences between miR-93-5p and FGD5. FGD5 presented low expression in breast cancer tissues and lower FGD5 expression in breast cancer patients corresponded to poorer prognosis. The expression levels between miR-93-5p and FGD5 were negatively correlated. Transfection of miR-93-5p inhibitor plasmid up-regulated the expression of FGD5 in TNBC cells. Dual luciferase reporter gene experiments confirmed that miR-93-5p could down-regulate the luciferase activity of wild-type FGD5. Conclusion The miR-93-5p can promote the invasion and migration of TNBC cells by targeting FGD5.