Dataset Information

LncRNA DANCR represses Doxorubicin-induced apoptosis through stabilizing MALAT1 expression in colorectal cancer cells.

ABSTRACT: Long non-coding RNA (lncRNA) DANCR has been reported to participate in key processes such as stem cell differentiation and tumorigenesis. In a high throughput screening for lncRNAs involved in Doxorubicin-induced apoptosis, we found DANCR was suppressed by Doxorubicin and it acted as an important repressor of apoptosis in colorectal cancer. Further studies demonstrated that DANCR promoted the oncogenic lncRNA MALAT1 expression via enhancing the RNA stability of MALAT1 to suppress apoptosis. MALAT1 could efficiently mediate the suppressive function of DANCR on apoptosis. Mechanistic studies found the RNA-binding protein QK served as an interacting partner of both DANCR and MALAT1, and the protein level of QK was subjected to the regulation by DANCR. Furthermore, QK was able to modulate the RNA stability of MALAT1, and the interaction between QK and MALAT1 was controlled by DANCR. In addition, QK could mediate the function of DANCR in regulating the expression of MALAT1 and suppressing apoptosis. These results revealed DANCR played a critical role in Doxorubicin-induced apoptosis in colorectal cancer cells, which was achieved by the interaction between DANCR and QK to enhance the expression of MALAT1.

SUBMITTER: Xiong M

PROVIDER: S-EPMC7791116 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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LncRNA DANCR represses Doxorubicin-induced apoptosis through stabilizing MALAT1 expression in colorectal cancer cells.

Xiong Minmin M Wu Mengshi M Dan Peng Huang Weijun W Chen Zehong Z Ke Haoxian H Chen Zewen Z Song Wu W Zhao Yonghua Y Xiang Andy P AP Zhong Xiaomin X

Cell death & disease 20210106 1

Long non-coding RNA (lncRNA) DANCR has been reported to participate in key processes such as stem cell differentiation and tumorigenesis. In a high throughput screening for lncRNAs involved in Doxorubicin-induced apoptosis, we found DANCR was suppressed by Doxorubicin and it acted as an important repressor of apoptosis in colorectal cancer. Further studies demonstrated that DANCR promoted the oncogenic lncRNA MALAT1 expression via enhancing the RNA stability of MALAT1 to suppress apoptosis. MALA ...[more]

PMID: 33414433

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Project description:BackgroundSpinal cord injury (SCI) is a neurological disease associated with a high disability rate. Low-dose lipopolysaccharide (LPS) has been reported to activate cross-immune tolerance and alleviate the effects of various traumatic stimuli. The present study aimed to explore the effect of LPS on SCI and the potential molecular mechanism.MethodsMale Sprague-Dawley (SD) rats were used to established an in vivo SCI model and were intraperitoneally injected with lentivirus particles encoding a MALAT1 small interfering RNA (siRNA) on day 10 prior to SCI and with 0.2 mg/kg LPS 72 h prior to SCI. Basso, Beattie, and Bresnahan (BBB) scoring; HE staining; and TUNEL assay were used to assess neurological function and pathophysiological changes. Western blot and immunohistochemistry (IHC) were used to detect cell autophagy and Nrf2 nuclear translocation. PC12 cells were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) to establish an in vitro SCI model. In vitro SCI model cells were pretreated with LPS and transfected with siMALAT1 or MALAT1 overexpression plasmid aimed at knocking down MALAT1 or overexpressing MALAT1. The cell counting kit-8 (CCK-8) assay was used to measure the toxicity of LPS towards PC12 cells. Flow cytometry and immunofluorescence analysis were performed to investigate cell apoptosis and Nrf2 nuclear translocation.ResultsSCI rats preconditioned with low-dose LPS had higher BBB scores, reduced SCI injury, increased MALAT1 expression and activated autophagy and Nrf2 nuclear translocation in the in vivo SCI model. In the in vitro SCI model, low-dose LPS treatment suppressed the apoptotic ratio of PC12 cells, increased MALAT1 expression, activated autophagy, and promoted Nrf2 nuclear translocation. Silencing MALAT1 exacerbated OGD/R injury in vitro and weakened the protective effect of low-dose LPS. Overexpression of MALAT1 inhibits OGD/R-induced apoptosis by inducing autophagy and promoting Nrf2 nuclear translocation. This was also been confirmed in animal experiments, silencing MALAT1 blocked the promotion of Nrf2 by low-dose LPS and the alleviated of SCI apoptosis.ConclusionsLow-dose LPS exhibited a protective role on SCI by activating autophagy and suppressing nerve cell apoptosis via the lncRNA MALAT1/Nrf2 axis.

Project description:PurposeWe aimed to identify and verify the key genes and lncRNAs associated with acute lung injury (ALI) and explore the pathogenesis of ALI. Research showed that lower expression of the lncRNA metastasis-associated lung carcinoma transcript 1 (MALAT1) alleviates lung injury induced by lipopolysaccharide (LPS). Nevertheless, the mechanisms of MALAT1 on cellular apoptosis remain unclear in LPS-stimulated ALI. We investigated the mechanism of MALAT1 in modulating the apoptosis of LPS-induced human pulmonary alveolar epithelial cells (HPAEpiC).MethodsDifferentially expressed lncRNAs between the ALI samples and normal controls were identified using gene expression profiles. ALI-related genes were determined by the overlap of differentially expressed genes (DEGs), genes correlated with lung, genes correlated with key lncRNAs, and genes sharing significantly high proportions of microRNA targets with MALAT1. Quantitative real-time PCR (qPCR) was applied to detect the expression of MALAT1, microRNA (miR)-194-5p, and forkhead box P2 (FOXP2) mRNA in 1 μg/ml LPS-treated HPAEpiC. MALAT1 knockdown vectors, miR-194-5p inhibitors, and ov-FOXP2 were constructed and used to transfect HPAEpiC. The influence of MALAT1 knockdown on LPS-induced HPAEpiC proliferation and apoptosis via the miR-194-5p/FOXP2 axis was determined using Cell counting kit-8 (CCK-8) assay, flow cytometry, and Western blotting analysis, respectively. The interactions between MALAT1, miR-194-5p, and FOXP2 were verified using dual-luciferase reporter gene assay.ResultsWe identified a key lncRNA (MALAT1) and three key genes (EYA1, WNT5A, and FOXP2) that are closely correlated with the pathogenesis of ALI. LPS stimulation promoted MALAT1 expression and apoptosis and also inhibited HPAEpiC viability. MALAT1 knockdown significantly improved viability and suppressed the apoptosis of LPS-stimulated HPAEpiC. Moreover, MALAT1 directly targeted miR-194-5p, a downregulated miRNA in LPS-stimulated HPAEpiC, when FOXP2 was overexpressed. MALAT1 knockdown led to the overexpression of miR-194-5p and restrained FOXP2 expression. Furthermore, inhibition of miR-194-5p exerted a rescue effect on MALAT1 knockdown of FOXP2, whereas the overexpression of FOXP2 reversed the effect of MALAT1 knockdown on viability and apoptosis of LPS-stimulated HPAEpiC.ConclusionOur results demonstrated that MALAT1 knockdown alleviated HPAEpiC apoptosis by competitively binding to miR-194-5p and then elevating the inhibitory effect on its target FOXP2. These data provide a novel insight into the role of MALAT1 in the progression of ALI and potential diagnostic and therapeutic strategies for ALI patients.

Dataset Information

LncRNA DANCR represses Doxorubicin-induced apoptosis through stabilizing MALAT1 expression in colorectal cancer cells.

Publications

LncRNA DANCR represses Doxorubicin-induced apoptosis through stabilizing MALAT1 expression in colorectal cancer cells.

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