Low level of exosomal long non-coding RNA <i>HOTTIP</i> is a prognostic biomarker in colorectal cancer

Oehme, Florian; Krahl, S; Győrffy, Balázs; Muessle, Benjamin; Rao, Venkatesh S.; Greif, Helena; Ziegler, Nicole; Lin, Kuailu; Thepkaysone, May-Linn; Polster, Heike; Tonn, Torsten; Schneider, Martin; Weitz, Juergen; Baenke, Franziska; Kahlert, Christoph

doi:10.1080/15476286.2019.1637697

Cited by 65 publications

(49 citation statements)

References 30 publications

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“…Mounting evidence has demonstrated that lncRNAs are closely associated with normal physiological progresses and pathological change [26]. The aberrantly expressed lncRNAs could be applied as prediction biomarkers for many diseases, including cancers [27][28][29]. In present study, we found that RHPN1-AS1, as a newly discovered lncRNA, was aberrantly up-regulated in CRC cells than non-tumor one.…”

Section: Discussionmentioning

confidence: 46%

Long noncoding RNA RHPN1-AS1 promotes colorectal cancer progression via targeting miR-7-5p/OGT axis

Zheng

Zhang

et al. 2020

Cancer Cell Int

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Background: Rhophilin Rho GTPase binding protein 1 antisense RNA 1 (RHPN1-AS1) is a newly discovered oncogene in several diseases, such as breast cancer, non-small cell lung cancer and uveal melanoma. Nevertheless, its molecular role in colorectal cancer (CRC) remains unknown. This paper explored the role of RHPN1-AS1 in CRC progression.Methods: qRT-PCR was used to detect relevant RNAs expression. CCK-8, EdU, flow cytometry, Transwell and western blot assays were performed to investigate the function of RHPN1-AS1 in CRC cells. Xenograft model was constructed to evaluate the effects of RHPN1-AS1 on tumor growth in vivo. Mechanical experiments were performed to investigate the relationship between relative genes.Results: RHPN1-AS1 was significantly overexpressed in CRC cell lines. Knockdown of RHPN1-AS1 could inhibit cell proliferation, while stimulating cell apoptosis in vitro. Cell migration and invasion abilities were greatly suppressed after silencing RHPN1-AS1. Besides, signal transducer and activator of transcription 3 (STAT3) served as transcription factor of RHPN1-AS1. Moreover, miR-7-5p was identified as a target of RHPN1-AS1 and was negatively regulated by RHPN1-AS1 in CRC. MiR-7-5p inhibition rescued the oncogenic function of RHPN1-AS1. Additionally, O-GlcNAcylation transferase (OGT) was the downstream target of miR-7-5p. OGT overexpression could abrogate the anti-tumor effects of RHPN1-AS1 knockdown on CRC.Conclusion: RHPN1-AS1 regulates CRC by mediating OGT through sponging miR-7-5p, suggesting that RHPN1-AS1 might be a potential therapeutic target for CRC.

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Section: Discussionmentioning

confidence: 46%

Long noncoding RNA RHPN1-AS1 promotes colorectal cancer progression via targeting miR-7-5p/OGT axis

Zheng

Zhang

et al. 2020

Cancer Cell Int

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“…A study focusing on circulating serum exosomes reported that the levels of lncRNA HOTTIP could predict OS of patients with CRC. Also, the expression levels of the same lncRNA could discriminate between CRC and healthy controls (AUC=0.75) 105. Expression levels of serum and tissue hsa_circ_0004585 correlated with CRC tumour size and this circRNA was proposed as a diagnostic biomarker (tissue: AUC=0.731, serum: AUC=0.707) 106.…”

Section: Ncrnas In Cell-to-cell Communication: the New Cancer Biomarkersmentioning

confidence: 99%

Non-coding RNAs in GI cancers: from cancer hallmarks to clinical utility

Dragomir

Kopetz

Ajani

et al. 2020

Gut

158

131

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One of the most unexpected discoveries in molecular oncology, in the last decades, was the identification of a new layer of protein coding gene regulation by transcripts that do not codify for proteins, the non-coding RNAs. These represent a heterogeneous category of transcripts that interact with many types of genetic elements, including regulatory DNAs, coding and other non-coding transcripts and directly to proteins. The final outcome, in the malignant context, is the regulation of any of the cancer hallmarks. Non-coding RNAs represent the most abundant type of hormones that contribute significantly to cell-to cell communication, revealing a complex interplay between tumour cells, tumour microenvironment cells and immune cells. Consequently, profiling their abundance in bodily fluids became a mainstream of biomarker identification. Therapeutic targeting of non-coding RNAs represents a new option for clinicians that is currently under development. This review will present the biology and translational value of three of the most studied categories on non-coding RNAs, the microRNAs, the long non-coding RNAs and the circular RNAs. We will also focus on some aspirational concepts that can help in the development of clinical applications related to non-coding RNAs, including using pyknons to discover new non-coding RNAs, targeting human-specific transcripts which are expressed specifically in the tumour cell and using non-coding RNAs to increase the efficiency of immunotherapy.

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“…103 Contrastingly in CRC, exosomal HOTTIP plays different roles. 104 Exosomes from CRC patients demonstrate lower expression level of HOTTIP than those from healthy individuals. As opposed to gastric cancer, patients with low level of exosomal HOTTIP have poor overall survival.…”

Section: E Xosomal Ln Crna S In C An Cer-clini C Al Appli C Ati On Smentioning

confidence: 94%

Biological functions and clinical applications of exosomal long non‐coding RNAs in cancer

Wang

Zhang

Zhou

2020

J Cellular Molecular Medi

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Exosomes are microvesicles that are derived from multivesicular bodies (MVBs) and released into the extracellular space upon fusion of MVBs with the plasma membrane. 1 Exosomes contain multiple components including lipids, proteins, RNA and DNA. Exosomes take part in the intercellular communication by transferring cargoes from donor cells to recipient cells. One of the cargoes of exosomes is long non-coding RNA (lncRNA). LncRNAs are RNA transcripts longer than 200 nt and have limited protein-coding potential. 2 LncRNAs are involved in numerous cellular processes. LncRNAs participate in the pathogenesis of many diseases, including cancer. 3 Lots of studies have demonstrated that lncRNAs regulate the malignant characteristics of cancer such as metastasis and drug resistance. Exosomal lncRNAs are RNA molecules, and exosomal lncRNAs acquired by recipient cells will exert their cancer-related roles in the recipient cells to regulate cancer progression. In this review, we summarize recent research regarding exosomal lncRNAs in cancers. We describe the biological roles of exosomal lncRNAs in cancer and discuss the potential clinical applications of exosomal lncRNAs in the future. 2 | E XOSOME S Exosomes are extracellular vesicles with a diameter of 30-100 nm and are released by multiple types of cells. 4-6 In the 1980s, exosomes

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Low level of exosomal long non-coding RNA HOTTIP is a prognostic biomarker in colorectal cancer

Cited by 65 publications

References 30 publications

Long noncoding RNA RHPN1-AS1 promotes colorectal cancer progression via targeting miR-7-5p/OGT axis

Long noncoding RNA RHPN1-AS1 promotes colorectal cancer progression via targeting miR-7-5p/OGT axis

Non-coding RNAs in GI cancers: from cancer hallmarks to clinical utility

Biological functions and clinical applications of exosomal long non‐coding RNAs in cancer

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