MALAT1 Is Associated with Poor Response to Oxaliplatin-Based Chemotherapy in Colorectal Cancer Patients and Promotes Chemoresistance through EZH2

Li, Peilong; Zhang, Xin; Wang, Haiyan; Wang, Lili; Liu, Tong; Li, Du; Yang, Yongmei; Wang, Chuanxin

doi:10.1158/1535-7163.mct-16-0591

Cited by 225 publications

(212 citation statements)

References 39 publications

(52 reference statements)

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“…It has been well‐formed that lncRNAs performed their cellular functions via controlling (including inhibiting or promoting) the expression of miRNAs, which in turn regulate their target genes and fulfils the actions of the whole pathways. In this study, we showed that MALAT1 interacts with DCP1A in SW480/SW620 CRC cells, which is consistent with previous research findings . Moreover, we found that enforced miR203 overexpression reversed the MALAT1 effects on CRC cell proliferation, aggression, and migration in vitro, and this process also increased the cell sensitivity to chemotherapy agents.…”

Section: Discussionsupporting

confidence: 92%

MALAT1 promotes the colorectal cancer malignancy by increasing DCP1A expression and miR203 downregulation

Zhu

Tao

et al. 2018

Molecular Carcinogenesis

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The long non-coding RNA MALAT1 has been proved to promote the cell proliferation, drug resistance, invasion, and metastasis of colorectal cancer (CRC) in vitro and in vivo by regulating the expression of various oncogenes and their protein products. Our previous work discovered that the expression of the mRNA-decapping enzymes 1a (DCP1A) is upregulated in CRCs. However, the relationships between MALAT1 and DCP1A in the development of CRC and the underlying mechanisms are still unclear. In this study, we investigated the molecular mechanisms by which MALAT1 and DCP1A may be linked to contribute to the malignancies of CRCs. We found that DCP1A is a direct target molecule of MALAT1. Moreover, by screening the downstream genes of MALAT1, we noticed that microRNA 203(miR203), an oncogene suppressor in numerous cancers, is inversely correlated to both MALAT1 and DCP1A expressions. Following MALAT1 knockdown, we observed overexpression of miR203 accompanied with DCP1A downregulation to a level that reversed the promoted cell proliferation, invasion, and migration in vitro and in vivo, which could be restored by miR203 knockdown or DCP1A overexpression. These results proposed a new molecular mechanism of MALAT-miR203-DCP1A axis which is involved with the development and contributes to the malignancy of colorectal cancers.

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Section: Discussionsupporting

confidence: 92%

MALAT1 promotes the colorectal cancer malignancy by increasing DCP1A expression and miR203 downregulation

Zhu

Tao

et al. 2018

Molecular Carcinogenesis

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“…Extensive efforts in the past have contributed to the understanding of both molecular and cellular mechanisms of noncoding RNAs in cancer progression, however, nearly all patients with lung cancer invariably become metastatic and chemoresistant [20]. Thus, novel molecular signatures seem to hold great promise in tumor characterization and could be used as potential prognostic markers and treatment target [21].…”

Section: Discussionmentioning

confidence: 99%

Circular RNA circPVT1 Promotes Proliferation and Invasion Through Sponging miR-125b and Activating E2F2 Signaling in Non-Small Cell Lung Cancer

Zhang

Jiang

et al. 2018

Cell Physiol Biochem

104

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Background/Aims: Circular RNAs (circRNAs) are key regulators in the development and progression of human cancers, however its role in non-small cell lung cancer (NSCLC) tumorigenesis is not well understood. The aim of this study is to identify the expression level of circPVT1 in NSCLC and further investigated its functional relevance with NSCLC progression both in vitro and in vivo. Methods: Quantative real-time PCR was used for the measurement of circPVT1 in NSCLC specimens and cell lines. Fluorescence in situ hybridization analysis (FISH) assay was used for the identification of sublocation of circPVT1 in NSCLC cells. Bioinformatics analysis, luciferase reporter assay and RNA immunoprecipitation (RIP) were performed to verify the binding of c-Fos at circPVT1 promoter region, and the direct interaction between circPVT1 and miR-125b. Gain- or loss-function assays were performed to evaluate the effects of circPVT1 on cell proliferation and invasion. Western blot and immunohistochemistry assays were performed to detect the protein levels involved in E2F2 pathway. Results: We found that circPVT1 was upregulated in NSCLC specimens and cells. The transcription factor c-Fos binded to the promoter region of circPVT1, resulting in the overexpression of circPVT1 in NSCLC. Knockdown of circPVT1 suppressed NSCLC cell proliferation, migration and invasion, and increased apoptosis. In addition, circPVT1 mediated NSCLC progression via the regulation of E2F2 signaling pathway. More importantly, circPVT1 was predominantly abundant in the cytoplasm of NSCLC cells, and circPVT1 could serve as a competing endogenous RNA to regulate E2F2 expression and tumorigenesis in a miR-125b-dependent manner, which is further verified by using an in vivo xenograft model. Conclusion: circPVT1 promotes NSCLC cell growth and invasion, and may serve as a promising therapeutic target for NSCLC patients. Therefore, silence of circPVT1 could be a future direction to develop a novel treatment strategy.

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“…In a study of response to chemo-resistant HCC cells, Yin et al identified 61 up-regulated and 59 down-regulated lnRNAs (fold change > 2, p < 0.05) associated with resistance [449]. Other lncRNAs identified include Linc00152 [151], SNHG5 [450], MALAT1 [451], CRNDE [452] and HULC [181]. Clearly, lncRNAs play important roles in resistance mechanisms to platinum-based drugs and could conceivably become therapeutic targets for re-sensitization strategies.…”

Section: Lncrnas Emt and Drug Resistancementioning

confidence: 99%

Long Non-Coding RNAs: Key Regulators of Epithelial-Mesenchymal Transition, Tumour Drug Resistance and Cancer Stem Cells

Heery

Finn

Cuffe

et al. 2017

Cancers

155

140

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Epithelial mesenchymal transition (EMT), the adoption by epithelial cells of a mesenchymal-like phenotype, is a process co-opted by carcinoma cells in order to initiate invasion and metastasis. In addition, it is becoming clear that is instrumental to both the development of drug resistance by tumour cells and in the generation and maintenance of cancer stem cells. EMT is thus a pivotal process during tumour progression and poses a major barrier to the successful treatment of cancer. Non-coding RNAs (ncRNA) often utilize epigenetic programs to regulate both gene expression and chromatin structure. One type of ncRNA, called long non-coding RNAs (lncRNAs), has become increasingly recognized as being both highly dysregulated in cancer and to play a variety of different roles in tumourigenesis. Indeed, over the last few years, lncRNAs have rapidly emerged as key regulators of EMT in cancer. In this review, we discuss the lncRNAs that have been associated with the EMT process in cancer and the variety of molecular mechanisms and signalling pathways through which they regulate EMT, and finally discuss how these EMT-regulating lncRNAs impact on both anti-cancer drug resistance and the cancer stem cell phenotype.

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MALAT1 Is Associated with Poor Response to Oxaliplatin-Based Chemotherapy in Colorectal Cancer Patients and Promotes Chemoresistance through EZH2

Cited by 225 publications

References 39 publications

MALAT1 promotes the colorectal cancer malignancy by increasing DCP1A expression and miR203 downregulation

MALAT1 promotes the colorectal cancer malignancy by increasing DCP1A expression and miR203 downregulation

Circular RNA circPVT1 Promotes Proliferation and Invasion Through Sponging miR-125b and Activating E2F2 Signaling in Non-Small Cell Lung Cancer

Long Non-Coding RNAs: Key Regulators of Epithelial-Mesenchymal Transition, Tumour Drug Resistance and Cancer Stem Cells

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