miR‐515‐5p controls cancer cell migration through<scp>MARK</scp>4 regulation

Pardo, Olivier E.; Castellano, Leandro; Munro, Catriona; Hu, Yili; Mauri, Francesco; Krell, Jonathan; Lara, Romain; Pinho, Filipa G.; Choudhury, Thameenah; Frampton, Adam E.; Pellegrino, Loredana; Pshezhetskiy, Dmitry; Wang, Yulan; Waxman, Jonathan; Seckl, Michael J.; Stebbing, Justin

doi:10.15252/embr.201540970

Cited by 97 publications

(86 citation statements)

References 25 publications

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“…5b and c). Simultaneously, we noticed that one of these candidate miRNAs, miR-515-5p, has been found to dramatically inhibit breast cancer cell proliferation and to control cancer cell migration through MARK4 regulation in breast cancer [42,43]. Therefore, we examined whether LINC00673 could interact with miR-515-5p to regulate MARK4.…”

Section: Linc00673 Regulates Mark4 Expression By Competing For Mir-51mentioning

confidence: 99%

LINC00673 is activated by YY1 and promotes the proliferation of breast cancer cells via the miR-515-5p/MARK4/Hippo signaling pathway

Qiao

Ning

Wan

et al. 2019

J Exp Clin Cancer Res

135

103

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Background An increasing number of studies have shown that long noncoding RNAs (lncRNAs) play essential roles in tumor initiation and progression. LncRNAs act as tumor promoters or suppressors by targeting specific genes via epigenetic modifications and competing endogenous RNA (ceRNA) mechanisms. In this study, we explored the function and detailed mechanisms of long intergenic nonprotein coding RNA 673 (LINC00673) in breast cancer progression. Methods Quantitative real-time PCR (qRT-PCR) was used to examine the expression of LINC00673 in breast cancer tissues and in adjacent normal tissues. Gain-of-function and loss-of function experiments were conducted to investigate the biological functions of LINC00673 in vitro and in vivo. We also explored the potential role of LINC00673 as a therapeutic target using antisense oligonucleotide (ASO) in vivo. RNA sequencing (RNA-seq), dual-luciferase reporter assays, chromatin immunoprecipitation (ChIP) assay, and rescue experiments were performed to uncover the detailed mechanism of LINC00673 in promoting breast cancer progression. Results In the present study, LINC00673 displayed a trend of remarkably increased expression in breast cancer tissues and was associated with poor prognosis in breast cancer patients. Importantly, LINC00673 depletion inhibited breast cancer cell proliferation by inhibiting the cell cycle and increasing apoptosis. Furthermore, ASO therapy targeting LINC00673 substantially suppressed breast cancer cell proliferation in vivo. Mechanistically, LINC00673 was found to act as a ceRNA by sponging miR-515-5p to regulate MARK4 expression, thus inhibiting the Hippo signaling pathway. Finally, ChIP assay showed that the transcription factor Yin Yang 1 (YY1) could bind to the LINC00673 promoter and increase its transcription in cis. Conclusions YY1-activated LINC00673 may exert an oncogenic function by acting as a sponge for miR-515-5p to upregulate the MARK4 and then inhibit Hippo signaling pathway, and may serve as a potential therapeutic target.

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Section: Linc00673 Regulates Mark4 Expression By Competing For Mir-51mentioning

confidence: 99%

LINC00673 is activated by YY1 and promotes the proliferation of breast cancer cells via the miR-515-5p/MARK4/Hippo signaling pathway

Qiao

Ning

Wan

et al. 2019

J Exp Clin Cancer Res

135

103

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“…Previous studies have uncovered the anti‐carcinogenic role of miR‐450b‐5p and miR‐515‐5p in some cancers, including in lung cancer 24‐27. Nonetheless, their specific functions in LUSC cells are still unclear, so we tested the effects of miR‐450b‐5p and miR‐515‐5p in LUSC cells.…”

Section: Resultsmentioning

confidence: 99%

H3K27ac‐activated LINC00519 promotes lung squamous cell carcinoma progression by targeting miR‐450b‐5p/miR‐515‐5p/YAP1 axis

Rusidanmu

et al. 2020

Cell Proliferation

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Objectives Long non‐coding RNAs (lncRNAs) are extensively reported as participants in the biological process of diverse malignancies, including lung squamous cell carcinoma (LUSC). Long intergenic non‐protein coding RNA 519 (LINC00519) is identified as a novel lncRNA which has not yet been studied in cancers. Materials and Methods LINC00519 expression was detected by qRT‐PCR. The effect of LINC00519 on LUSC cellular activities was determined by in vitro and in vivo assays. Subcellular fractionation and FISH assays were conducted to identify the localization of LINC00519. The interaction between miR‐450b‐5p/miR‐515‐5p and LINC00519/YAP1 was verified by RIP, RNA pull‐down and luciferase reporter assays. Results Elevated level of LINC00519 was identified in LUSC tissues and cell lines. High LINC00519 level predicted unsatisfactory prognosis. Then, loss‐of‐function assays suggested the inhibitive role of silenced LINC00519 in cell proliferation, migration, invasion and tumour growth and promoting effect on cell apoptosis in LUSC. Mechanically, LINC00519 was activated by H3K27 acetylation (H3K27ac). Moreover, LINC00519 sponged miR‐450b‐5p and miR‐515‐5p to up‐regulate Yes1 associated transcriptional regulator (YAP1). Additionally, miR‐450b‐5p and miR‐515‐5p elicited anti‐carcinogenic effects in LUSC. Finally, rescue assays validated the effect of LINC00519‐miR‐450b‐5p‐miR‐515‐5p‐YAP1 axis in LUSC. Conclusions H3K27ac‐activated LINC00519 acts as a competing endogenous RNA (ceRNA) to promote LUSC progression by targeting miR‐450b‐5p/miR‐515‐5p/YAP1 axis.

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“…There have also been multiple reports on the role of miR‐486 in tumorigenesis, some concluding that it acts as a tumor suppressor of LUSC . miR‐515 has also been reported as a tumor suppressor, and similarly, studies have shown that miR‐512 not only inhibits glycolysis but also accelerates apoptosis . So far, there are few reports of a role for miR‐516 or miR‐525 in LUSC, however, there is evidence that they can regulate target genes in other tumors to affect protein expression .…”

Section: Discussionmentioning

confidence: 99%

MicroRNAs associated with lung squamous cell carcinoma: New prognostic biomarkers and therapeutic targets

Gao

Feng

et al. 2019

J of Cellular Biochemistry

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Background With the development in research, the importance of microRNAs (miRNAs) in the occurrence and metastasis, and prognosis of lung squamous cell carcinoma (LUSC) have received extensive attention. This study aims to identify new biomarkers and pivotal genes associated with LUSC prognosis through bioinformatics. Materials and methods We downloaded miRNA and messenger RNA samples related to LUSC from The Cancer Genome Atlas (TCGA) database. Following initial data screening and preprocessing, we utilized the R platform and a range of analysis tools (miRDB, TargetScanHuman7.2, DAVID, and Cytoscape_v3.5.1) to analyze the TCGA data and identify highly specific and sensitive biomarkers. Results We finally identified 12 miRNAs and six central genes closely related to the overall survival of patients with LUSC. We found that high expression of 7 miRNAs (miR‐301b, miR‐383, miR‐512, miR‐515, miR‐525, miR‐577, and miR‐5682) and low expression of five miRNAs (miR‐448, miR‐486, miR‐4732,miR‐4732, miR‐516, and miR‐1911) can significantly improve the overall survival rate of patients with LUSC. The six central genes DLGAP5, CENPA, CHEK1, LRRK2, CALB1, and TOP2A are directly or indirectly involved in the formation and metastasis of LUSC and could, therefore, be considered as target genes for drug therapy. Conclusion With the development in research, the importance of miRNAs in the occurrence and metastasis and prognosis of LUSC have received extensive attention. This study aims to identify new biomarkers and pivotal genes associated with LUSC prognosis through bioinformatics.

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miR‐515‐5p controls cancer cell migration throughMARK4 regulation

Cited by 97 publications

References 25 publications

LINC00673 is activated by YY1 and promotes the proliferation of breast cancer cells via the miR-515-5p/MARK4/Hippo signaling pathway

LINC00673 is activated by YY1 and promotes the proliferation of breast cancer cells via the miR-515-5p/MARK4/Hippo signaling pathway

H3K27ac‐activated LINC00519 promotes lung squamous cell carcinoma progression by targeting miR‐450b‐5p/miR‐515‐5p/YAP1 axis

MicroRNAs associated with lung squamous cell carcinoma: New prognostic biomarkers and therapeutic targets

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