Dataset Information

Long noncoding RNA MAPKAPK5-AS1 promotes colorectal cancer progression by cis-regulating the nearby gene MK5 and acting as a let-7f-1-3p sponge.

ABSTRACT:

Background

Long noncoding RNAs (lncRNAs) are considered critical regulators in cancers; however, the clinical significance and mechanisms of MAPKAPK5-AS1 (hereinafter referred to as MK5-AS1) in colorectal cancer (CRC) remain mostly unknown.

Methods

In this study, quantitative real-time PCR (qPCR) and western blotting were utilized to detect the levels of MK5-AS1, let-7f-1-3p and MK5 (MAPK activated protein kinase 5) in CRC tissues and cell lines. The biological functions of MK5-AS1, let-7f-1-3p and MK5 in CRC cells were explored using Cell Counting Kit-8 (CCK8), colony formation and transwell assays. The potential mechanisms of MK5-AS1 were evaluated by RNA pull-down, RNA immunoprecipitation (RIP), dual luciferase reporter assay, chromatin immunoprecipitation (ChIP) and bioinformatics analysis. The effects of MK5-AS1 and MK5 on CRC were investigated by a xenotransplantation model.

Results

We confirmed that MK5-AS1 was significantly increased in CRC tissues. Knockdown of MK5-AS1 suppressed cell migration and invasion in vitro and inhibited lung metastasis in mice. Mechanistically, MK5-AS1 regulated SNAI1 expression by sponging let-7f-1-3p and cis-regulated the adjacent gene MK5. Moreover, MK5-AS1 recruited RBM4 and eIF4A1 to promote the translation of MK5. Our study verified that MK5 promoted the phosphorylation of c-Jun, which activated the transcription of SNAI1 by directly binding to its promoter.

Conclusions

MK5-AS1 cis-regulated the nearby gene MK5 and acted as a let-7f-1-3p sponge, playing a vital role in CRC tumorigenesis. This study could provide novel insights into molecular therapeutic targets of CRC.

SUBMITTER: Yang T

PROVIDER: S-EPMC7370515 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Publications

Long noncoding RNA MAPKAPK5-AS1 promotes colorectal cancer progression by cis-regulating the nearby gene MK5 and acting as a let-7f-1-3p sponge.

Yang Ting T Chen Wei-Cong WC Shi Pei-Cong PC Liu Man-Ru MR Jiang Tao T Song Hu H Wang Jia-Qi JQ Fan Rui-Zhi RZ Pei Dong-Sheng DS Song Jun J

Journal of experimental & clinical cancer research : CR 20200720 1

<h4>Background</h4>Long noncoding RNAs (lncRNAs) are considered critical regulators in cancers; however, the clinical significance and mechanisms of MAPKAPK5-AS1 (hereinafter referred to as MK5-AS1) in colorectal cancer (CRC) remain mostly unknown.<h4>Methods</h4>In this study, quantitative real-time PCR (qPCR) and western blotting were utilized to detect the levels of MK5-AS1, let-7f-1-3p and MK5 (MAPK activated protein kinase 5) in CRC tissues and cell lines. The biological functions of MK5-AS ...[more]

PMID: 32690100

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Project description:PSMA3 antisense RNA 1 (PSMA3‑AS1), a long noncoding RNA, promotes the progression of esophageal squamous cell carcinoma. However, no study to date has explored the expression or roles of PSMA3‑AS1 in non‑small cell lung carcinoma (NSCLC). The present study examined the expression profile and role of PSMA3‑AS1 in NSCLC. It also aimed to identify how PSMA3‑AS1 promotes the malignant phenotype of NSCLC cells. PSMA3‑AS1 expression in NSCLC tissues and cell lines was measured by reverse transcription‑quantitative polymerase chain reaction. Cell Counting Kit‑8, cell apoptosis, Transwell migration and invasion, and xenograft tumor assays were conducted to study the effects of PSMA3‑AS1 on the aggressive phenotype of NSCLC cells. Furthermore, bioinformatics analysis, RNA immunoprecipitation, luciferase reporter assay, western blotting, and rescue experiments were used to elucidate the interaction among PSMA3‑AS1, microRNA‑409‑3p (miR‑409‑3p), and spindlin 1 (SPIN1) in NSCLC cells. In the present study, high levels of PSMA3‑AS1 were confirmed in both NSCLC tissues and cell lines. An increased PSMA3‑AS1 level was correlated with advanced tumor‑node‑metastasis stage and increased lymph node metastasis. Patients with NSCLC with high PSMA3‑AS1 levels had shorter overall survival than those with low PSMA3‑AS1 levels. PSMA3‑AS1 depletion significantly decreased NSCLC cell proliferation, migration, and invasion, as well as substantially increased cell apoptosis in vitro. Furthermore, PSMA3‑AS1 deficiency decreased NSCLC tumor growth in vivo. Through molecular mechanism assays, it was revealed that PSMA3‑AS1 acted as a molecular sponge for miR‑409‑3p and consequently increased SPIN1 expression. Notably, rescue experiments revealed that the inhibition of miR‑409‑3p or restoration of SPIN1 expression abrogated the effects of PSMA3‑AS1 knockdown in NSCLC cells. Collectively, PSMA3‑AS1 functioned as an oncogenic long noncoding RNA in NSCLC. PSMA3‑AS1 sponged miR‑409‑3p and thus increased SPIN1 expression, promoting the aggressive phenotype of NSCLC cells.

Project description:BackgroundLong non-coding RNAs (lncRNAs) are widely involved in human cancers' progression by regulating tumor cells' various malignant behaviors. MAPKAPK5-AS1 has been recognized as an oncogene in colorectal cancer. However, the biological role of MAPKAPK5-AS1 in hepatocellular carcinoma (HCC) has not been explored.MethodsQuantitative real-time PCR was performed to detect the level of MAPKAPK5-AS1 in HCC tissues and cell lines. The effects of MAPKAPK5-AS1 on tumor growth and metastasis were assessed via in vitro experiments, including MTT, colony formation, EdU, flow cytometry, transwell assays, and nude mice models. The western blotting analysis was carried out to determine epithelial-mesenchymal transition (EMT) markers and AKT signaling. The interaction between MAPKAPK5-AS1, miR-154-5p, and PLAGL2 were explored by luciferase reporter assay and RNA immunoprecipitation. The regulatory effect of HIF-1α on MAPKAPK5-AS1 was evaluated by chromatin immunoprecipitation.ResultsMAPKAPK5-AS1 expression was significantly elevated in HCC, and its overexpression associated with malignant clinical features and reduced survival. Functionally, MAPKAPK5-AS1 knockdown repressed the proliferation, mobility, and EMT of HCC cells and induced apoptosis. Ectopic expression of MAPKAPK5-AS1 contributed to HCC cell proliferation and invasion in vitro. Furthermore, MAPKAPK5-AS1 silencing suppressed, while MAPKAPK5-AS1 overexpression enhanced HCC growth and lung metastasis in vivo. Mechanistically, MAPKAPK5-AS1 upregulated PLAG1 like zinc finger 2 (PLAGL2) expression by acting as an endogenous competing RNA (ceRNA) to sponge miR-154-5p, thereby activating EGFR/AKT signaling. Importantly, rescue experiments demonstrated that the miR-154-5p/PLAGL2 axis mediated the function of MAPKAPK5-AS1 in HCC cells. Interestingly, we found that hypoxia-inducible factor 1α (HIF-1α), a transcript factor, could directly bind to the promoter to activate MAPKAPK5-AS1 transcription. MAPKAPK5-AS1 regulated HIF-1α expression through PLAGL2 to form a hypoxia-mediated MAPKAPK5-AS1/PLAGL2/HIF-1α signaling loop in HCC.ConclusionsOur results reveal a MAPKAPK5-AS1/PLAGL2/HIF-1α signaling loop in HCC progression and suggest that MAPKAPK5-AS1 could be a potential novel therapeutic target of HCC.

Dataset Information

Long noncoding RNA MAPKAPK5-AS1 promotes colorectal cancer progression by cis-regulating the nearby gene MK5 and acting as a let-7f-1-3p sponge.

Background

Methods

Results

Conclusions

Publications

Long noncoding RNA MAPKAPK5-AS1 promotes colorectal cancer progression by cis-regulating the nearby gene MK5 and acting as a let-7f-1-3p sponge.

Similar Datasets

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