Long non-coding antisense RNA KRT7-AS is activated in gastric cancers and supports cancer cell progression by increasing KRT7 expression

Huang, Bing; Song, Jee Hoon; Cheng, Yulan; Abraham, John M.; Ibrahim, Sariat; Sun, Zhenguo; Ke, Xia; Meltzer, Stephen J.

doi:10.1038/onc.2016.25

Cited by 126 publications

(112 citation statements)

References 44 publications

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“…Our findings provide important insights into CRC pathogenesis, and are expected to facilitate the development of approaches for early diagnosis and targeted therapy of CRC based on lncRNAs. Recent investigations have revealed that antisense transcripts can exert effects via inducing their neighbouring protein-coding genes [60-62]. However, whether SH3PXD2A-AS1 can modulate SH3PXD2A and other possible target genes is still unclear, and the underlying mechanisms have not yet been explored in this study.…”

Section: Discussionmentioning

confidence: 77%

Long Non-Coding RNA SH3PXD2A-AS1 Promotes Cell Progression Partly Through Epigenetic Silencing P57 and KLF2 in Colorectal Cancer

Peng

Zhou

et al. 2018

Cell Physiol Biochem

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Background/Aims: Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies worldwide. Current evidence has revealed the key roles of long non-coding RNAs (IncRNAs) in multiple cancers, including CRC. In this study we identified the lncRNA SH3PXD2A-AS1 as a novel molecule associated with CRC progression by analyzing the publicly available data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) assays were performed to examine the expression levels of SH3PXD2A-AS1 in CRC tissue samples and CRC cell lines. Cell viability examination, colony-formation experiments, ethynyl deoxyuridine (Edu) assays and flow cytometry were performed to investigate the roles of SH3PXD2A-AS1 in CRC proliferation, cell cycle regulation, and apoptosis. Transwell assays were used to explore the effects of SH3PXD2A-AS1 on CRC cells migration and invasion. A nude mice model was used to assess the effects of SH3PXD2A-AS1 on tumorigenesis in vivo. Subcellular fractionation, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (ChIP) assays were conducted to detect the molecular mechanisms of SH3PXD2A-ASl-mediated gene expression. Rescue assays were used to determine whether P57 and Kruppel-like factor 2 (KLF2) were involved in SH3PXD2A-ASl-dependent CRC proliferation. Results: We firstly found that SH3PXD2A-AS1 was significantly upregulated in CRC tissues and cell lines, and overexpression of SH3PXD2A-AS1 was correlated with tumor size, TNM stage, and lymph node metastasis in patients with CRC. Furthermore, SH3PXD2A-AS1 knockdown inhibited CRC cells proliferation, migration and invasion in vitro, and suppressed tumorigenesis in vivo. Mechanistic studies indicated that SH3PXD2A-AS1 could epiqenetically repress P57 and KLF2 expression through interaction with EZH2. Rescue experiments suggested that SH3PXD2A-ASl-mediated oncogenesis was impaired by overexpression of P57 or KLF2. Interestingly, the expression of SH3PXD2A-AS1 was inversely correlated with the expression of P57 and KLF2 in CRC tissue samples. Conclusion: Our research presents the first evidence that SH3PXD2A-AS1 acts as an oncogene in CRC, and may be a promising diagnostic or therapeutic target in patients with CRC.

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Section: Discussionmentioning

confidence: 77%

Long Non-Coding RNA SH3PXD2A-AS1 Promotes Cell Progression Partly Through Epigenetic Silencing P57 and KLF2 in Colorectal Cancer

Peng

Zhou

et al. 2018

Cell Physiol Biochem

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“…Knockdown of CASC9 in ESCC cells reduced their migration and invasion. In an investigation of gastric adenocarcinomas, levels of lncRNA KRT7-AS were significantly higher in tumors than in matched normal adjacent gastric tissues 51 . This lncRNA contains regions that are antisense to the protein-coding keratin 7 gene ( KRT7 ); surprisingly, RNA hybrids formed between these transcripts increase expression of KRT7 mRNA and protein.…”

Section: Lncrnas In Be and Eacmentioning

confidence: 95%

Long Noncoding RNAs in the Pathogenesis of Barrett’s Esophagus and Esophageal Carcinoma

Abraham

Meltzer

2017

Gastroenterology

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For many years, only a small fraction of the human genome was believed to regulate cell function and development. This protein-coding portion composed only 1% to 2% of 3 billion human DNA base pairs— the remaining sequence was classified as junk DNA. Subsequent research has revealed that most of the genome is transcribed into a broad array of noncoding RNAs, ranging in size from microRNA (20–23 nucleotides) to long noncoding RNA (lncRNA, more than 200 nucleotides). These noncoding RNA classes have been shown to use diverse molecular mechanisms to control gene expression and organ system development. As anticipated, alterations in this large control system can contribute to disease pathogenesis and carcinogenesis. We review the involvement of noncoding RNAs—lncRNAs in particular—in development of Barrett's esophagus and esophageal carcinoma.

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“…Specifically, yeast work revealed that caloric restriction activates the R-loop suppressing proteins Rnh1/201 (yeast RNaseH1/2) and Pif1 (ATP-dependent RNA helicase) [15,45]. RNaseH enzymes can degrade the RNA component of RNA-DNA hybrids within R-loops [46,47].…”

Section: Wide-ranging Molecular Functions Of Ataxin-2mentioning

confidence: 99%

Ataxin-2: From RNA Control to Human Health and Disease

Ostrowski

Hall

Mekhail

2017

Genes

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RNA-binding proteins play fundamental roles in the regulation of molecular processes critical to cellular and organismal homeostasis. Recent studies have identified the RNA-binding protein Ataxin-2 as a genetic determinant or risk factor for various diseases including spinocerebellar ataxia type II (SCA2) and amyotrophic lateral sclerosis (ALS), amongst others. Here, we first discuss the increasingly wide-ranging molecular functions of Ataxin-2, from the regulation of RNA stability and translation to the repression of deleterious accumulation of the RNA-DNA hybrid-harbouring R-loop structures. We also highlight the broader physiological roles of Ataxin-2 such as in the regulation of cellular metabolism and circadian rhythms. Finally, we discuss insight from clinically focused studies to shed light on the impact of molecular and physiological roles of Ataxin-2 in various human diseases. We anticipate that deciphering the fundamental functions of Ataxin-2 will uncover unique approaches to help cure or control debilitating and lethal human diseases.

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Long non-coding antisense RNA KRT7-AS is activated in gastric cancers and supports cancer cell progression by increasing KRT7 expression

Cited by 126 publications

References 44 publications

Long Non-Coding RNA SH3PXD2A-AS1 Promotes Cell Progression Partly Through Epigenetic Silencing P57 and KLF2 in Colorectal Cancer

Long Non-Coding RNA SH3PXD2A-AS1 Promotes Cell Progression Partly Through Epigenetic Silencing P57 and KLF2 in Colorectal Cancer

Long Noncoding RNAs in the Pathogenesis of Barrett’s Esophagus and Esophageal Carcinoma

Ataxin-2: From RNA Control to Human Health and Disease

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