NORAD accelerates chemo-resistance of non-small-cell lung cancer via targeting at miR-129-1-3p/SOX4 axis.
Ontology highlight
ABSTRACT:
SUBMITTER: Huang Q
PROVIDER: S-EPMC6981097 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Small nucleolar RNA host gene 17 (SNHG17), a novel functional long noncoding RNA, has been demonstrated to play an essential role in the oncogenesis of several tumors. However, for esophageal squamous cell carcinoma (ESCC) the expression pattern and detailed function of SNHG17 are largely unknown. Hence, we conducted this study to explore potential roles and underlying oncogenic mechanisms for SNHG17 in ESCC progression. Results demonstrated SNHG17 to be markedly upregulated in ESCC. Knockdown of SNHG17 significantly suppressed ESCC cell proliferation, invasion, and epithelial-mesenchymal transition in vitro and tumor growth in vivo. Online database software analysis found miR-338-3p to interact with SNHG17 with the level of miR-338-3p negatively correlated with SNHG17 levels in ESCC samples. Further, miR-338-3p was found to directly target SRY-box transcription factor 4 (SOX4) in ESCC cells. Mechanistic analysis suggested that SNHG17 acts as an endogenous "sponge" competing with miR-338-3p to regulate SOX4, thereby promoting tumor progression. These results suggest that these molecular interactions may be potential therapeutic targets for ESCC.
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Project description:Background:The long noncoding RNA (lncRNA) JPX is a molecular switch for X-chromosome inactivation. Accumulating studies have shown that the aberrant expression and function of lncRNAs are involved in the occurrence and development of tumors. However, the functional importance and mechanism of the action of lncRNA JPX in cervical cancer (CC) remain unknown. Method:In this study, qRT-PCR and western blotting were used to evaluate the mRNA or protein expression of JPX, miR-25-3p and SOX4 in CC tissues and cell lines. StarBase v2.0 database, luciferase reporter assay and RNA immunoprecipitation assay were used to explore the relationship between JPX and miR-25-3p. EdU assay, CCK-8 assay and transwell assay were utilized to evaluate the proliferation, migration and invasion of CC cells. The tumor xenograft assay in nude mice was performed to demonstrate the role of the JPX/miR-25-3p/SOX4 axis in CC. Results:We found that JPX was markedly upregulated, whereas miR-25-3p was markedly downregulated in CC tissues and cell lines, and the expression of JPX was negatively correlated with miR-25-3p in CC tissues. Moreover, overexpression of JPX increased proliferation, migration and invasion of HeLa cells, whereas knockdown of JPX decreased proliferation, migration and invasion of HeLa cells. In contrast to JPX, overexpression of miR-25-3p decreased proliferation, migration and invasion of HeLa cells. In addition, knockdown of JPX was found to inhibit HeLa cell viability and tumor development via up-regulating the expression of miR-25-3p and inhibiting the expression of SOX4. Conclusions:Our study demonstrates that JPX promotes cervical cancer progression through modulating the miR-25-3p/SOX4 axis, and may serve as a potential target for CC therapy.
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Project description:We aimed to explore the interaction among lncRNA MALAT1, miR-129 and SOX2. Besides, we would investigate the effect of MALAT1 on the proliferation of glioma stem cells and glioma tumorigenesis. Differentially expressed lncRNAs in glioma cells and glioma stem cells were screened out with microarray analysis. The targeting relationship between miR-129 and MALAT1 or SOX2 was validated by dual-luciferase reporter assay. The expressions of MALAT1, miR-129 and SOX2mRNA in both glioma non-stem cells and glioma stem cells were examined by qRT-PCR assay. The impact of MALAT1 and miR-129 on glioma stem cell proliferation was observed by CCK-8 assay, EdU assay and sphere formation assay. The protein expression of SOX2 was determined by western blot. The effects of MALAT1 and miR-129 on glioma tumour growth were further confirmed using xenograft mouse model. The mRNA expression of MALAT1 was significantly up-regulated in glioma stem cells compared with non-stem cells, while miR-129 was significantly down-regulated in glioma stem cells. MALAT1 knockdown inhibited glioma stem cell proliferation via miR-129 enhancement. Meanwhile, miR-129 directly targeted at SOX2 and suppressed cell viability and proliferation of glioma stem cells by suppressing SOX2 expression. The down-regulation of MALAT1 and miR-129 overexpression both suppressed glioma tumour growth via SOX2 expression promotion in vivo. MALAT1 enhanced glioma stem cell viability and proliferation abilities and promoted glioma tumorigenesis through suppressing miR-129 and facilitating SOX2 expressions.
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Project description:Mounting evidence suggests the vital roles of long noncoding RNA (lncRNAs) in the glioma. However, the role of LINC00511 in gliomagenesis is still uncovered. Here, in this study, we aim to investigate the effects of LINC00511 on the glioma cancer phenotype and its deepgoing mechanism. Results indicated that LINC00511 was up-regulated in glioma tissues and cell lines, moreover its overexpression positively correlated with the poor prognosis and advanced pathological stages. For the upstream regulation, LINC00511 was epigenetically up-regulated by transcription factor specificity protein 1 (SP1). Gain and loss of functional experiments demonstrated that LINC00511 promoted the proliferation and invasion of glioma cells in vitro. The knockdown of LINC00511 repressed the tumour growth in vivo. Mechanistically, LINC00511 positively regulated the CCND2 expression via competitively sponging with miR-124-3p. Overall, our finding illuminates that LINC00511 is induced by SP1 and accelerates the glioma progression through targeting miR-124-3p/CCND2 axis, constructing the SP1/LINC00511/miR-124-3p/CCND2 axis.
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Project description:Histone deacetylase inhibitors (HDACis) are the recommended treatment for many solid tumors; however, resistance is a major clinical obstacle for their efficacy. High levels of the transcription factor nuclear factor erythroid 2 like-2 (Nrf2) in cancer cells suggest a vital role in chemoresistance, and regulation of autophagy is one mechanism by which Nrf2 mediates chemoresistance. Although the molecular mechanisms underlying this activity are unclear, understanding them may ultimately improve therapeutic outcomes following HDACi treatment. In this study, we found that HDACi treatment increased Nrf2 mRNA and protein levels and enhanced Nrf2 transcriptional activity. Conversely, Nrf2 knockdown or inhibition blocked HDACi-induced autophagy. In addition, a microRNA (miRNA) array identified upregulation of miR-129-3p in response to Nrf2 overexpression. Chromatin immunoprecipitation assays confirmed miR-129-3p to be a direct Nrf2 target. RepTar and RNAhybrid databases indicated mammalian target of rapamycin (mTOR) as a potential miR-129-3p target, which we experimentally confirmed. Finally, Nrf2 inhibition or miR-129-3p in combination with HDACis increased cell death in vitro and in vivo. Collectively, these results demonstrated that Nrf2 regulates mTOR during HDACi-induced autophagy through miRNA-129-3p and inhibition of this pathway could enhance HDACi-mediated cell death.
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Project description:Background:Thyroid cancer is an endocrine malignancy that is growing in incidence worldwide. Despite progress in diagnostics and treatment of thyroid cancer, prognosis remains poor. Emerging research has shown that circular RNAs (circRNAs) have crucial regulatory roles in cancers. However, the possible functions and mechanisms of hsa_circ_0011385 remain undetermined. Materials and methods:Expression levels of hsa_circ_0011385 and miR-361-3p were evaluated by qRT-PCR assay. The interaction between hsa_circ_0011385 and miR-361-3p was verified by dual-luciferase reporter assay. Effects of hsa_circ_0011385 or miR-361-3p on cell viability, proliferation, cell cycle, apoptosis, migration and invasion were confirmed by cell counting kit-8 (CCK-8), carboxyfluoresceinsuccinimidyl ester (CFSE), flow cytometry, and Transwell assays in vitro. The effect of hsa_circ_0011385 on thyroid cancer progression was also determined by in vivo tumor formation assay. Target genes of miR-361-3p were predicted by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and the expression of apoptosis- and metastasis-related proteins were assessed by Western blot assay. Results:Hsa_circ_0011385 upregulated in thyroid cancer; hsa_circ_0011385 knockdown inhibited thyroid cancer cell proliferation, migration and invasion, and promoted cell cycle arrest and apoptosis. In addition, hsa_circ_0011385 could negatively regulate miR-361-3p by functioning as a sponge. Hsa_circ_0011385 promoted thyroid cancer cell proliferation, migration and invasion and suppressed cell cycle arrest and apoptosis by targeting miR-361-3p in vitro. We also found that hsa_circ_0011385 knockdown dramatically inhibited thyroid cancer growth in vivo. Furthermore, hsa_circ_0011385 regulated expression of apoptosis and metastasis-related proteins in thyroid cancer. Conclusions:Hsa_circ_0011385facilitated thyroid cancer cell proliferation, invasion and migration, and inhibited thyroid cancer cell cycle arrest and apoptosis by targeting miR-361-3p, suggesting that the hsa_circ_0011385/miR-361-3p axis might be a promising therapeutic target for thyroid cancer.
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Project description:Primary cilium serves as a cellular “antenna” to sense environmental signals. Ciliogenesis requires the removal of CP110 to convert the mother centriole into the basal body. Actin dynamics is also critical for cilia formation. How these distinct processes are properly regulated remains unknown. Here we show that miR-129-3p, a microRNA conserved in the vertebrates, controlled cilia assembly by down-regulating both CP110 and four proteins critical for actin dynamics, Arp2, Toca1, abLIM1, and abLIM3. Consistently, blocking miR-129-3p repressed cilia formation in cultured mammalian cells, whereas its overexpression potently induced ciliogenesis in proliferating cells and extraordinary cilia elongation. Moreover, inhibition of miR-129-3p in zebrafish embryos suppressed cilia assembly in the Kupffer’s vesicle and pronephric duct, leading to developmental abnormalities including curved body, pericardial oedema, and randomised left-right patterning. Our results thus unravel a novel mechanism that orchestrates both the centriole-to-basal body transition and subsequent cilia assembly via microRNA-mediated posttranscriptional regulations. We want to find the targets of miR-129-3p by overexpressing miR-129-3p oligo or control oligo in hTERT-RPE1 cells. Through microarray analysis we could check the downregulated genes and these genes might be the targets of miR-129-3p.
2012-06-01 | GSE34846 | GEO
Project description:Several reports have proposed that lncRNAs, as potential biomarkers, participate in the progression and growth of malignant tumors. HIF1A-AS2 is a novel lncRNA and potential biomarker, involved in the genesis and development of carcinomas. However, the molecular mechanism of HIF1A-AS2 in renal carcinoma is unclear. The relative expression levels of HIF1A-AS2 and miR-30a-5p were detected using RT-qPCR in renal carcinoma tissues and cell lines. Using loss-of-function and overexpression, the biological effects of HIF1A-AS2 and miR-30a-5p in kidney carcinoma progression were characterized. Dual luciferase reporter gene analysis and Western blot were used to detect the potential mechanism of HIF1A-AS2 in renal carcinomas. HIF1A-AS2 was upregulated in kidney carcinoma tissues when compared with para-carcinoma tissues (P < 0.05). In addition, tumor size, tumor node mestastasis stage and differentiation were identified as being closely associated with HIF1A-AS2 expression (P < 0.05). Knockdown or overexpression of HIF1A-AS2 either restrained or promoted the malignant phenotype and WNT/β-catenin signaling in renal carcinoma cells (P < 0.05). MiR-30a-5p was downregulated in renal cancers and partially reversed HIF1A-AS2 functions in malignant renal tumor cells. HIF1A-AS2 acted as a microRNA sponge that actively regulated the relative expression of SOX4 in sponging miR-30a-5p and subsequently increased the malignant phenotypes of renal carcinomas. HIF1A-AS2 showed a carcinogenic effect and miR-30a-5p acted as an antagonist of the anti-oncogene effects in the pathogenesis of renal carcinomas. The HIF1A-AS2-miR-30a-5p-SOX4 axis was associated with the malignant progression and development of renal carcinoma. The relative expression of HIF1A-AS2 was negatively correlated with the expression of miR-30a-5p, and was closely correlated with SOX4 mRNA levels in renal cancers.
| S-EPMC8185866 | biostudies-literature
Project description:Primary cilium serves as a cellular M-bM-^@M-^\antennaM-bM-^@M-^] to sense environmental signals. Ciliogenesis requires the removal of CP110 to convert the mother centriole into the basal body. Actin dynamics is also critical for cilia formation. How these distinct processes are properly regulated remains unknown. Here we show that miR-129-3p, a microRNA conserved in the vertebrates, controlled cilia assembly by down-regulating both CP110 and four proteins critical for actin dynamics, Arp2, Toca1, abLIM1, and abLIM3. Consistently, blocking miR-129-3p repressed cilia formation in cultured mammalian cells, whereas its overexpression potently induced ciliogenesis in proliferating cells and extraordinary cilia elongation. Moreover, inhibition of miR-129-3p in zebrafish embryos suppressed cilia assembly in the KupfferM-bM-^@M-^Ys vesicle and pronephric duct, leading to developmental abnormalities including curved body, pericardial oedema, and randomised left-right patterning. Our results thus unravel a novel mechanism that orchestrates both the centriole-to-basal body transition and subsequent cilia assembly via microRNA-mediated posttranscriptional regulations. We want to find the targets of miR-129-3p by overexpressing miR-129-3p oligo or control oligo in hTERT-RPE1 cells. Through microarray analysis we could check the downregulated genes and these genes might be the targets of miR-129-3p. RPE1 cells were transfected with control (Ctrl) or miR-129-3p (M129) oligo for 72h, and harvested for RNA extraction and hybridization on Affymetrix microarrays. Two samples: RPE1-Ctrl, RPE1-M129
2012-05-31 | E-GEOD-34846 | biostudies-arrayexpress