Knockdown of Long Non-coding RNA HOTAIR Suppresses Tumor Invasion and Reverses Epithelial-mesenchymal Transition in Gastric Cancer

Xu, Zhiyuan; Qian, Yu; Du, Ye; Yang, Lifen; Dong, Ruizeng; Huang, Ling; Yu, Pengfei; Cheng, Xiangdong

doi:10.7150/ijbs.6339

Cited by 224 publications

(221 citation statements)

References 23 publications

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“…Several lncRNAs have been associated with outcome in solid tumors (29)(30)(31)(32)(33)(34). However, to our knowledge, there are no published reports for hematological malignancies, including AML.…”

Section: Discussionmentioning

confidence: 80%

“…HOTAIR modulates chromatin structures by serving as a scaffold and recruiting histone modifiers (28). In breast cancer, HOTAIR promotes cancer cell invasion and metastasis in vivo through epigenetic silencing of metastasis suppressor genes (29)(30)(31)(32)(33). In patients with nonsmall cell lung cancer, high expression of the lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was associated with metastases and poor survival, indicating its importance as a prognostic biomarker (34).…”

Section: Significancementioning

confidence: 99%

“…LncRNAs have emerged as important regulators of gene expression, showing cell-specific expression patterns and subcellular localization and are involved in many biological roles including imprinting, epigenetic regulation, apoptosis, and cell cycle (26,27). The well-characterized lncRNA HOX transcript antisense RNA (HOTAIR) has been found to be up-regulated in multiple cancers including breast, colorectal, hepatic, gastric, and pancreatic cancers (28)(29)(30)(31)(32)(33). HOTAIR modulates chromatin structures by serving as a scaffold and recruiting histone modifiers (28).…”

Section: Significancementioning

confidence: 99%

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Expression and prognostic impact of lncRNAs in acute myeloid leukemia

Garzon

Volinia

Papaioannou

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

212

193

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Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides, located within the intergenic stretches or overlapping antisense transcripts of protein coding genes. LncRNAs are involved in numerous biological roles including imprinting, epigenetic regulation, apoptosis, and cell cycle. To determine whether lncRNAs are associated with clinical features and recurrent mutations in older patients (aged ≥60 y) with cytogenetically normal (CN) acute myeloid leukemia (AML), we evaluated lncRNA expression in 148 untreated older CN-AML cases using a custom microarray platform. An independent set of 71 untreated older patients with CN-AML was used to validate the outcome scores using RNA sequencing. Distinctive lncRNA profiles were found associated with selected mutations, such as internal tandem duplications in the FLT3 gene (FLT3-ITD) and mutations in the NPM1, CEBPA, IDH2, ASXL1, and RUNX1 genes. Using the lncRNAs most associated with event-free survival in a training cohort of 148 older patients with CN-AML, we derived a lncRNA score composed of 48 lncRNAs. Patients with an unfavorable compared with favorable lncRNA score had a lower complete response (CR) rate [P < 0.001, odds ratio = 0.14, 54% vs. 89%], shorter disease-free survival (DFS) [P < 0.001, hazard ratio (HR) = 2.88] and overall survival (OS) (P < 0.001, HR = 2.95). The validation set analyses confirmed these results (CR, P = 0.03; DFS, P = 0.009; OS, P = 0.009). Multivariable analyses for CR, DFS, and OS identified the lncRNA score as an independent marker for outcome. In conclusion, lncRNA expression in AML is closely associated with recurrent mutations. A small subset of lncRNAs is correlated strongly with treatment response and survival

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Section: Discussionmentioning

confidence: 80%

Section: Significancementioning

confidence: 99%

Section: Significancementioning

confidence: 99%

See 1 more Smart Citation

Expression and prognostic impact of lncRNAs in acute myeloid leukemia

Garzon

Volinia

Papaioannou

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

212

193

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“…Furthermore, the expression of Snail, one of the major transcription factors regulating EMT, could be induced by HOTAIR overexpression, implying that HOTAIR could act as a potential regulator of EMT. 80 It is possible that other lncRNAs could be important during EMT or could act as regulators of other EMT-related genes. In addition, it is possible that lncRNAs could be involved in the complex interplay between tumor cells and the tumor stroma or that they could also influence inflammatory cell behavior.…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNAs in cancer invasion and metastasis

Shen

Pan

2015

Modern Pathology

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Recent large-scale transcriptome analyses have revealed that the human genome contains more than just protein-coding genes. Indeed, a large number of transcripts, including long non-coding RNAs (lncRNAs), lack protein-coding capacity, and increasing evidence suggests that lncRNAs could have a critical role in the regulation of diverse cellular processes, such as stem cell pluripotency, development, cell growth and apoptosis, and cancer invasion and/or metastasis. Furthermore, the aberrant expression of several lncRNAs is closely linked to cancer invasion and/or metastasis. Although the underlying molecular mechanisms by which lncRNAs regulate cancer invasion and/or metastasis are not clearly understood, recent studies have revealed that aberrant lncRNAs expression affects the progression of cancer. In this review, we highlight recent findings regarding the roles of lncRNAs in cancer invasion and/or metastasis.

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“…11,16 In fact, previous studies have shown that particular deregulated lncRNAs are important regulators of tumor formation and progression. 17,24 For example, the antisense intergenic RNA HOX Antisense Intergenic RNA (HOTAIR) is highly expressed in multiple types of primary somatic tumors, such as hepatocellular carcinoma, 25,26 pancreatic cancer, 27 and gastric cancer, 28 as well as some metastatic tumors, including metastatic breast tumors 29 and melanoma. 30 Moreover, high HOTAIR level is associated with poor patient survival rate 20,27 and tumor recurrence.…”

Section: Lncrnas In Cancermentioning

confidence: 99%

Long non-coding RNAs in colorectal cancer: implications for pathogenesis and clinical application

Pan

2014

Modern Pathology

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Long non-coding RNAs (lncRNAs) are a class of newly identified non-coding RNA molecules that are emerging as key regulators of tumor initiation and development. Colorectal cancer (CRC) remains a major health problem worldwide, and there remains a need to further refine the current screening approaches as well as provide tailored diagnostic and therapeutic approaches. Multiple dysregulated lncRNAs participate in tumorigenesis through a variety of molecular mechanisms, and various regulatory factors frequently contribute to the aberrant expression of lncRNAs in CRC, thereby allowing malignant transformation. Additionally, the association of dysregulated lncRNAs with specific developmental stages and clinical outcomes indicates their potential as strong diagnostic and prognostic predictors as well as therapeutic targets. Here we provide a brief overview of the known functions of CRC-associated lncRNAs, describe some potential molecular mechanisms that underlie changes in lncRNA expression in CRC, and attempt to uncover their clinical and therapeutic potential. Keywords: colorectal cancer; diagnosis; dysregulation; long non-coding RNA; prognosis High-throughput genome-scale studies have demonstrated that more than 93% of the DNA sequences in the human genome are actively transcribed. 1 However, only approximately 5-10% of the sequences are stably transcribed into mRNA or non-coding RNA (ncRNA). Genome tiling arrays have revealed that the amount of non-coding sequence is at least four times larger than the amount of coding sequence, which indicates that only 1% of the human genome is composed of protein-coding genes and the remaining 4-9% is transcribed into ncRNAs. 2 Therefore, ncRNAs constitute a very large proportion of the total RNA molecules.The function and clinical significance of short regulatory ncRNAs, such as microRNAs (miRNAs) and small interfering RNAs (siRNAs), were elucidated first, 3 and the regulatory roles of miRNAs have been broadly recognized in almost all physiological and pathological processes in the body, including carcinogenesis. 4 For example, we previously reported that MIR95 promotes cell proliferation and targets sorting nexin 1 in human colorectal carcinoma; 5 moreover, in colorectal cancer (CRC) patients, the plasma levels of MIR29a and MIR92a are significantly upregulated and the plasma levels of MIR601 and MIR760 are significantly downregulated; thus the levels of these miRNAs have good diagnostic value for CRC screening. 6,7 According to their transcript size, ncRNAs are grouped into two major classes: (i) small ncRNAs with transcripts o200 nucleotides (nt; eg, aforementioned siRNAs and miRNAs, Piwi-interacting RNAs, and some retrotransposon-derived RNAs) and (ii) long non-coding RNAs (lncRNAs), this class includes five broad categories: sense, antisense, bidirectional, intronic, and intergenic, based on the proximity between neighboring transcripts. 8 For a time, lncRNAs was commonly defined as a proteincoding transcripts that is 4200 nt. 9 However, this definition is arbitrary and ...

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Knockdown of Long Non-coding RNA HOTAIR Suppresses Tumor Invasion and Reverses Epithelial-mesenchymal Transition in Gastric Cancer

Cited by 224 publications

References 23 publications

Expression and prognostic impact of lncRNAs in acute myeloid leukemia

Expression and prognostic impact of lncRNAs in acute myeloid leukemia

Long non-coding RNAs in cancer invasion and metastasis

Long non-coding RNAs in colorectal cancer: implications for pathogenesis and clinical application

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