1,770,863 research outputs found
miR-515-5p controls cancer cell migration through MARK4 regulation
No full textHere, we show that miR-515-5p inhibits cancer cell migration and metastasis. RNA-seq analyses of both oestrogen receptor receptor-positive and receptor-negative breast cancer cells overexpressing miR-515-5p reveal down-regulation of NRAS, FZD4, CDC42BPA, PIK3C2B and MARK4 mRNAs. We demonstrate that miR-515-5p inhibits MARK4 directly 3' UTR interaction and that MARK4 knock-down mimics the effect of miR-515-5p on breast and lung cancer cell migration. MARK4 overexpression rescues the inhibitory effects of miR-515-5p, suggesting miR-515-5p mediates this process through MARK4 down-regulation. Furthermore, miR-515-5p expression is reduced in metastases compared to primary tumours derived from both in vivo xenografts and samples from patients with breast cancer. Conversely, miR-515-5p overexpression prevents tumour cell dissemination in a mouse metastatic model. Moreover, high miR-515-5p and low MARK4 expression correlate with increased breast and lung cancer patients' survival, respectively. Taken together, these data demonstrate the importance of miR-515-5p/MARK4 regulation in cell migration and metastasis across two common cancers
MiR-515-5p was a direct target of hsa_circ_0056686.
No full text(A) The sequences of hsa_circ_0056686 containing the miR-515-5p binding sites or mutant binding sites were showed. (B) (n = 30) Relative miR-515-5p expression level in ULM tissues and normal myometrial tissues. (C) The luciferase activity was tested after transfecting hsa_circ_0056686-wt and hsa_circ_0056686-mut. (D) RNA pull down assay was performed to detect the enrichment of hsa_circ_0056686 in the Bio-miR-515-5p-wt group and Bio-probe-NC group. (E) The expression of miR-515-5p was detected after overexpressing or silencing hsa_circ_0056686. (F) The sequences of miR-515-5p containing the AKAP13 binding sites or mutant binding sites were showed. *P vs normal myometrial tissues (B), NC mimic (C), Bio-probe-NC (D), vector or sh-NC (E).</p
miR-515-5p controls cancer cell migration through MARK4 regulation
Get PDFHere we show that miR-515-5p inhibits cancer cell migration and metastasis. RNA-seq
analyses of both estrogen receptor-positive and negative breast cancer cells overexpressing
miR-515-5p reveals down-regulation of NRAS, FZD4, CDC42BPA, PIK3C2B
and MARK4 mRNAs. We demonstrate that miR-515-5p inhibits MARK4 directly 3’UTR
interaction and that MARK4 knockdown mimics the effect of miR-515-5p on breast and
lung cancer cell migration. MARK4 over-expression rescues the inhibitory effects of miR-
515-5p, suggesting miR-515-5p mediates this process through MARK4 down-regulation.
Furthermore, miR-515-5p expression is reduced in metastases compared to primary
tumours derived from both in vivo xenografts and samples from patients with breast
cancer. Conversely, miR-515-5p overexpression prevents tumour cell dissemination in
a mouse metastatic model. Moreover, high miR-515-5p and low MARK4 expression
correlate with increased breast and lung cancer patients’ survival, respectively. Taken
together, these data demonstrate the importance of miR-515-5p/MARK4 regulation in
cell migration and metastasis across two common cancers
Participant 515 Community Conversations Interview
No full textIn this interview, Participant 515 shares they have suffered from COVID-19 along with a few family members. The participant expresses that they wish everyone would have taken the pandemic more seriously early on to better contain transmission. They say their workplace offers COVID-19 testing and they rely on the news to get COVID-19-related information. The participant also shares their views on the COVID-19 vaccine.New Jersey Department of Healt
Downregulation of microRNA-515-5p by the estrogen receptor modulates sphingosine kinase 1 and breast cancer cell proliferation
No full textSphingosine kinase 1 (SK1) plays an important role in estrogen-dependent breast tumorigenesis, but its regulation is poorly understood. A subset of microRNAs (miRNA, miR) is regulated by estrogen and contributes to cellular proliferation and cancer progression. Here, we describe that miR-515-5p is transcriptionally repressed by estrogen receptor a (ERa) and functions as a tumor suppressor in breast cancer. Its downregulation enhances cell proliferation and estrogen-dependent SK1 activity, mediated by a reduction of miR-515-5p posttranscriptional repression. Enforced expression of miR-515-5p in breast cancer cells causes a reduction in SK1 activity, reduced cell proliferation, and the induction of caspase-dependent apoptosis. Conversely, opposing effects occur with miR-515-5p inhibition and by SK1 silencing. Notably, we show that estradiol (E2) treatment downregulates miR-515-5p levels, whereas the antiestrogen tamoxifen causes a decrease in SK1, which is rescued by silencing miR-515-5p. Analysis of chromatin immunoprecipitation sequencing (ChIP-Seq) data reveals that miR-515-5p suppression is mediated by a direct interaction of ERa within its promoter. RNA-sequencing (RNA-Seq) analysis of breast cancer cells after overexpressing miR-515-5p indicates that it partly modulates cell proliferation by regulating the Wnt pathway. The clinical implications of this novel regulatory system are shown as miR-515-5p is significantly downregulated in ER-positive (n = 146) compared with ER-negative (n = 98) breast cancers. Overall, we identify a new link between ERa, miR-515-5p, proliferation, and apoptosis in breast cancer tumorigenesis
Depletion of circPDSS1 inhibits ITGA11 production to confer cisplatin sensitivity through miR-515-5p in gastric cancer
No full textChemoresistance limits cisplatin (DDP)-mediated treatment for gastric cancer (GC). Circular RNA (circRNA) acts an important role in chemoresistance. However, the underlying mechanism of circPDSS1 regulating DDP sensitivity in GC remains unclear. The expression patterns of circPDSS1, miR-515-5p and integrin subunit alpha 11 (ITGA11) were analyzed by qRT-PCR. Protein expression was checked by Western blotting analysis. Cell viability was investigated by 3-(4,5-dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell proliferation was evaluated by colony formation assay and 5-ethynyl-2′-deoxyuridine (EdU) assay. The analysis of cell apoptosis, migration and invasion was performed by flow cytometry analysis and transwell assays. Dual-luciferase reporter assay and RNA immunoprecipitation assay were conducted to identify the associations among circPDSS1, miR-515-5p and ITGA11. In vivo assay was implemented using a xenograft mouse model assay. CircPDSS1 and ITGA11 expression were significantly upregulated, whereas miR-515-5p was downregulated in DDP-resistant GC tissues and cells in comparison with controls. CircPDSS1 depletion reduced DDP resistance, cell proliferation, migration and invasion but induced cell apoptosis in DDP-resistant GC cells. CircPDSS1 directly bound to miR-515-5p. CircPDSS1-mediated actions were dependent on the regulation of miR-515-5p. Besides, miR-515-5p was associated with ITGA11, and circPDSS1 regulated ITGA11 expression by binding to miR-515-5p. Overexpression of miR-515-5p improved DDP sensitivity owing to the downregulation of ITGA11. Further, circPDSS1 mediated DDP sensitivity by regulating miR-515-5p and ITGA11 in vivo. CircPDSS1 conferred DDP resistance through the miR-515-5p/ITGA11 axis in GC cells.</p
Hsa_circ_0056686 exerted the tumor-promoting ability of CAFs by directly targeting miR-515-5p.
No full textCAFssh-circ_0056686-CM treated LSMCs were transfected with miR-515-5p mimic or miR-515-5p inhibitor, respectively. (A) The migration ability of LSMCs was detected by Transwell assay. (B) The apoptosis ratio of LSMCs was detected by flow cytometry assay. (C) The expression of apoptosis-related proteins Cleaved-caspase3 and Bcl-2 was examined. (D) The expression of ERS-related proteins GRP78, CHOP and ATF6 was examined. (E) The expression of ECM-related proteins COL1A1, COL1A2 and COL3A1 was examined. *P vs CAFssh-NC-CM or CAFssh-NC-CM + NC mimic.</p
Long non-coding RNA DLGAP1-AS1 promotes the progression of gastric cancer via miR-515-5p/MARK4 axis
No full textLong non-coding RNA (lncRNA) is an essential regulator of carcinogenesis and cancer progression. In the study, we explored the role of lncRNA DLGAP1-AS1 in gastric cancer (GC). qRT-PCR was carried out to detect DLGAP1-AS1 expression in GC tissues and cell lines. CCK-8 assay, EdU assay, and transwell experiments were employed to detect the malignant biological behaviors of GC cells with DLGAP1-AS1 knockdown or overexpression. Bioinformatics and dual-luciferase report assay were used to confirm the binding relationship between DLGAP1-AS1 and miR-515-5p. MARK4 expression was detected by western blot after DLGAP1-AS1/miR-515-5p was selectively regulated. DLGAP1-AS1 was up-regulated in GC tissues and cell lines, and its high expression was closely associated with larger tumor size, higher TNM stage, and lymph node metastasis. Furthermore, DLGAP1-AS1 overexpression enhanced cell proliferation, migration, and invasion, and miR-515-5p could reverse these effects. DLGAP1-AS1 participated in the regulation of the MARK4 signaling pathway by targeting miR-515-5p. DLGAP1-AS1 promoted GC progression through miR-515-5p/MARK4 signaling pathway.</div
Circular RNA circ-LARP1B contributes to cutaneous squamous cell carcinoma progression by targeting microRNA-515-5p/TPX2 microtubule nucleation factor axis
No full textCircular RNAs (circRNAs) have shown pivotal regulatory roles in tumorigenesis and progression. Our purpose was to analyze the role of circRNA La ribonucleoprotein 1B (circ-LARP1B; hsa_circ_0070934) in cutaneous squamous cell carcinoma (CSCC) progression and its associated mechanism. Cell viability, colony formation ability, migration, and invasion were analyzed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide (MTT) assay, colony formation assay, wound healing assay, and transwell invasion assay. Flow cytometry was performed to analyze cell apoptosis and cell cycle progression. Cell glycolytic metabolism was analyzed using Glucose Uptake Colorimetric Assay kit, Lactate Assay Kit II, and ATP colorimetric Assay kit. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to verify the interaction between microRNA-515-5p (miR-515-5p) and circ-LARP1B or TPX2 microtubule nucleation factor (TPX2). Circ-LARP1B expression was up-regulated in CSCC tissues and cell lines. Circ-LARP1B knockdown suppressed cell viability, colony formation ability, migration, invasion, cell cycle progression, and glycolysis and triggered cell apoptosis in CSCC cells. miR-515-5p was a direct target of circ-LARP1B in CSCC cells, and circ-LARP1B silencing-mediated anti-tumor effects were largely counteracted by miR-515-5p knockdown. miR-515-5p directly interacted with the 3ʹ untranslated region (3ʹUTR) of TPX2. TPX2 overexpression largely overturned miR-515-5p-mediated anti-tumor effects in CSCC cells. Circ-LARP1B could up-regulate TPX2 expression by sponging miR-515-5p in CSCC cells. Circ-LARP1B knockdown suppressed tumor growth in vivo. In conclusion, circ-LARP1B contributed to CSCC progression by targeting miR-515-5p/TPX2 axis. The circ-LARP1B/miR-515-5p/TPX2 axis might provide novel therapeutic targets for CSCC patients.</p
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