MiR-9-5p Promotes Lung Adenocarcinoma Cell Proliferation, Migration and Invasion by Targeting ID4
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ABSTRACT:
SUBMITTER: Zhu K
PROVIDER: S-EPMC8564129 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Accumulating evidence has indicated that long noncoding RNAs (lncRNAs) play pivotal roles in the processes of cancer occurrence, progression, and treatment. FAM83A-AS1 is a novel onco-lncRNA involved in various cancers. Nevertheless, the biological function and underlying mechanism of FAM83A-AS1 in lung adenocarcinoma (LUAD) remain largely unclear. In this study, we found FAM83A-AS1 to be upregulated in LUAD tissues and closely associated with tumor size, lymph node metastasis, and TNM stage. In addition, high FAM83A-AS1 expression correlated positively with a poor prognosis. Functional investigation revealed that FAM83A-AS1 promotes LUAD cell proliferation, migration, invasion and the epithelial-mesenchymal transition (EMT) in vitro and tumor growth in vivo. Mechanistically, FAM83A-AS1 functions as an endogenous sponge of miR-150-5p by directly targeting it, removing inhibition of MMP14, a target of miR-150-5p. Furthermore, rescue assays demonstrated that FAM83A-AS1 enhances cell migration, invasion and EMT by modulating the miR-150-5p/MMP14 pathway. Collectively, we conclude that the novel FAM83A-AS1/miR-150-5p/MMP14 axis regulates LUAD progression, suggesting an innovative therapeutic strategy for this cancer.
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Project description:Triple-negative breast cancer (TNBC) is the most aggressive subtypes of breast cancer, which has few effective targeted therapies. Various sources of evidence confirm that microRNAs (miRNAs) contribute to the progression and metastasis of human breast cancer. However, the molecular mechanisms underlying the changes in miRNAs expression and the regulation of miRNAs functions have not been well clarified. In this study, we found that the expression of miR-30b-5p was upregulated in breast cancer tissues and breast cancer cell lines, compared to paracancer tissues and normal breast cell lines. Moreover, induced overexpression of miR-30b-5p promoted the MDA-MB-231 and HCC 1937 cell growth, migration, and invasion and reduced the cellular apoptosis. Further studies confirmed that miR-30b-5p could directly target ASPP2 and then activate the AKT signaling pathway. Our results suggested that miR-30b-5p could act as a tumor promoter in TNBC. The newly identified miR-30b-5p/ASPP2/AKT axis represents a novel therapeutic strategy for treating TNBC.
| S-EPMC7210518 | biostudies-literature
Project description:ObjectiveWe aimed to investigate the mechanism of the regulatory axis of miR-196b/AQP4 underlying the invasion and migration of lung adenocarcinoma (LUAD) cells.MethodsLUAD miRNA and mRNA expression profiles were downloaded from TCGA database and then differential analysis was used to identify the target miRNA. Target gene for the miRNA was obtained via prediction using 3 bioinformatics databases and intersection with the differentially expressed mRNAs searched from TCGA-LUAD. Then, qRT-PCR and western blot were used to validate the expression of miR-196b and AQP4. Dual-luciferase reporter assay was performed to confirm the targeting relationship between miR-196b and AQP4. Transwell assay was used to investigate the migration and invasion of LUAD cells.ResultsMiR-196b was screened out by differential and survival analyses, and the downstream target gene AQP4 was identified. In LUAD, miR-196b was highly expressed while AQP4 was poorly expressed. Besides, overexpression of miR-196b promoted cell invasion and migration, while overexpression of AQP4 had negative effects. Moreover, the results of the dual-luciferase reporter assay suggested that AQP4 was a direct target of miR-196b. In addition, we also found that overexpressing AQP4 could suppress the promotive effect of miR-196b on cancer cell invasion and migration.ConclusionMiR-196b promotes the invasion and migration of LUAD cells by down-regulating AQP4, which helps us find new molecular targeted therapies for LUAD.
| S-EPMC8097310 | biostudies-literature
Project description:BackgroundIt is increasingly evidenced that long non-coding RNAs (lncRNAs) play an important role in various diseases. LncRNA LINC01194 acts as an oncogene in several cancer types. Nevertheless, the role of LINC01194 in lung adenocarcinoma (LUAD) has not yet been revealed.MethodsqRT-PCR was used to detect the expression of LINC01194, miR-641 and SETD7 mRNA, while western blot was exploited to examine SETD7 protein level. Cell proliferation was detected by colony formation and EdU assays. Transwell assays detected cell migration and invasion. TUNEL assay and flow cytometry analysis were used to detect cell apoptosis. RIP, RNA pull down and luciferase reporter assays detected the binding among LINC01194, miR-641 and SETD7.ResultsLINC01194 was significantly upregulated in LUAD tissues and cell lines. Knockdown of LINC01194 resulted in decreased cell proliferation, migration and invasion, and increased apoptosis. Mechanistic experiments unveiled that LINC01194 augmented SETD7 expression in LUAD cells by competitively interacting with miR-641. Rescue experiments showed that miR-641 inhibition and SETD7 overexpression rescued the repressing impacts on LUAD cell proliferation, migration and invasion caused by LINC01194 knockdown.ConclusionLINC01194 promotes the progression of LUAD by enhancing miR-641-targeted SETD7. The LINC01194/miR-641/SETD7 axis might provide new molecular targets for treating LUAD.
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Project description:BackgroundNon-small cell lung cancer (NSCLC) includes lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). MicroRNA (miRNA) plays an important role in the regulation of post-transcriptional gene expression in animals and plants, especially in lung adenocarcinoma.MethodsMiR-1307-5p is an miRNA with significant differences screened by the second generation of high-throughput sequencing in the early stage of our research group. In the current study, a series of in vitro and in vivo experiments were carried out. MiR-1307-5p mimic, miR-1307-5p inhibitor, and NC were transfected into A549 and H1299 lung adenocarcinoma cells. The correlation between miR-1307-5p and clinicopathological features in pathological samples was analyzed using a lung adenocarcinoma tissue microarray, and miR-1307-5p expression was detected by qPCR. CCK-8, EdU, colony formation, scratch test, and Transwell assays were used to observe cell proliferation and migration. Double luciferase assay, western blot, qPCR, and immunohistochemistry were employed in confirming the target relationship between miR-1307-5p and TRAF3. Western blotting was used to analyze the relationship between miR-1307-5p and the NF-κB/MAPK pathway. Finally, the effect of miR-1307-5p on tumor growth was studied using a subcutaneous tumorigenesis model in nude mice.ResultsIncreased miR-1307-5p expression was significantly related to decreased overall survival rate of lung adenocarcinoma patients, revealing miR-1307-5p as a potential oncogene in lung adenocarcinoma. MiR-1307-5p mimic significantly promoted while miR-1307-5p inhibitor reduced the growth and proliferation of A549 and H1299 cells. MiR-1307-5p overexpression significantly enhanced the migration ability while miR-1307-5p inhibition reduced the migration ability of A549 and H1299 cells. Target binding of miR-1307-5p to TRAF3 was confirmed by double luciferase assay, western blot, qPCR, and immunohistochemistry. miR-1307-5p caused degradation of TRAF3 mRNA and protein. MiR-1307-5p targeted TRAF3 and activated the NF-κB/MAPK pathway. TRAF3 colocalized with p65 and the localization of TRAF3 and p65 changed in each treatment group. Tumor volume of the lv-miR-1307-5p group was significantly larger than that of the lv-NC group, and that of the lv-miR-1307-5p-inhibitor group was significantly smaller than that of the lv-NC group.ConclusionIn conclusion, miR-1307-5p targets TRAF3 and activates the NF-κB/MAPK pathway to promote proliferation in lung adenocarcinoma.
| S-EPMC7552495 | biostudies-literature
Project description:BackgroundExtensive studies revealed that long non-coding RNAs (lncRNAs) could act as a regulator in tumors, including lung adenocarcinoma (LUAD). LncRNA FTX transcript, XIST regulator (FTX) has been reported to regulate the biological behaviors of some cancers. Nevertheless, its functional role and molecular mechanism remain obscure in LUAD. Our current study concentrates on exploring the biological function of FTX in LUAD.MethodsRT-qPCR was used to test the expression of FTX, miR-335-5p or NUCB2 in LUAD cells. The effect of FTX on LUAD progression was investigated by colony formation, EdU, flow cytometry, TUNEL, transwell and western blot assays. The interaction between microRNA-335-5p (miR-335-5p) and FTX or nucleobindin 2 (NUCB2) was confirmed by luciferase reporter assay.ResultsRT-qPCR showed that FTX expression was up-regulated in LUAD cell lines. Loss-of-function assay indicated that FTX accelerated cell proliferation, migration and invasion, while inhibited cell apoptosis in LUAD. Besides, miR-335-5p, lowly expressed in LUAD cells, was discovered to be sponged by FTX. Subsequently, NUCB2 was identified as a target gene of miR-335-5p. Additionally, it was confirmed that NUCB2 functioned as an oncogene in LUAD. Rescue assays indicated that LUAD progression inhibited by FTX knockdown could be restored by NUCB2 up-regulation.ConclusionFTX played an oncogenic role in LUAD and contributed to cancer development via targeting miR-335-5p/NUCB2 axis.
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Project description:Lung cancer is the most common cancer in males and females and ~40% of lung cancer cases are adenocarcinomas. Previous studies have demonstrated that myristoylated alanine rich protein kinase C substrate (MARCKS) is upregulated in several types of cancer and is associated with poor prognosis in patients with breast cancer. However, its expression level and role in lung adenocarcinoma remain unknown. Therefore, the aim of the present study was to investigate the expression level and biological functions of MARCKS like 1 (MARCKSL1), a member of the MARCKS family, in lung adenocarcinoma. The expression level of MARCKSL1 was examined in human lung adenocarcinoma tissues and cell lines. MARCKSL1-specific small interfering RNAs effectively suppressed its expression level and significantly inhibited the proliferation, migration and invasion of lung adenocarcinoma cells. Additionally, the role of MARCKSLI in the regulation of metastasis was examined. Silencing MARCKSL1 decreased the expression of the epithelial-mesenchymal transition (EMT)-associated proteins E-cadherin, N-cadherin, vimentin and snail family transcriptional repressor 2, and decreased the phosphorylation level of AKT. The results obtained in the current study suggested that MARCKSL1 promoted the progression of lung adenocarcinoma by regulating EMT. MARCKSLI may have prognostic value and serve as a novel therapeutic target in lung adenocarcinoma.
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Project description:It has previously been reported that lung cancer has the highest morbidity and mortality rate worldwide; however, the pathogenesis underlying lung cancer has not been fully elucidated. The aim of the present was primarily to assess the influence of microRNA (miR)-106a-5p on the biological behaviors of lung cancer cells. In the present study, bioinformatics analysis was used to analyze the expression characteristics of miR-106a-5p and its relationship with the prognosis of patients with lung adenocarcinoma (LUAD) in The Cancer Genome Atlas. A dual luciferase reporter assay was performed to verify the binding of miR-106a-5p and liver kinase B1 (LKB1). The Cell Counting Kit-8, colony formation and Transwell assays were utilized to detect cell viability, proliferation and migration, respectively. Protein and RNA expression levels were examined by western blotting and reverse transcription-quantitative PCR analysis, respectively. It was observed that miR-106a-5p was highly expressed in LUAD and associated with poor prognosis. miR-106a-5p promoted the proliferation and migration of LUAD cells, and inhibited autophagy. By contrast, LKB1 inhibited cell proliferation and migration, promoted autophagy and blocked the cancer-promoting effects of miR-106a-5p. Overexpression of miR-106a-5p inhibited the phosphorylation of AMP-activated protein kinase (AMPK) and tuberin (TSC2), and promoted the phosphorylation of mTOR. By contrast, overexpression of LKB1 blocked the promotion of mTOR phosphorylation, and the inhibition of AMPK and TSC2 phosphorylation caused by miR-106a-5p. In summary, the results of the present study indicated that miR-106a-5p regulated the phosphorylation of the AMPK pathway by targeting LKB1, and was involved in the proliferation, migration and autophagy of LUAD cells.
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