Antisense Transcription in the Mammalian Transcriptome

Katayama, Shintaro; Tomaru, Yuji; Kasukawa, Takeya; Waki, Kazunori; Nakanishi, Misato; Nakamura, Mari; Nishida, Hiromi; Yap, Chui-Sun; Suzuki, Masanori; Kawai, Jun; Suzuki, Harukazu; Carninci, Piero; Hayashizaki, Yoshihide; Wells, Christine A.; Frith, Martin C.; Ravasi, Timothy; Pang, Ken C; Hallinan, Jennifer; Mattick, John S.; Hume, David; Lipovich, Leonard; Batalov, Serge; Engström, Pär G.; Mizuno, Yosuke; Faghihi, Mohammad Ali; Sandelin, Albin; Chalk, Alistair M.; Mottagui‐Tabar, Salim; Zhong, Ling; Lenhard, Boris; Wahlestedt, Claes

doi:10.1126/science.1112009

Cited by 1,522 publications

(803 citation statements)

References 26 publications

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“…Antisense lncRNAs may form sense‐antisense pairs by pairing with a protein‐coding gene on the opposite strand and subsequently regulating epigenetic silencing, transcription, and mRNA stability 25, 26, 27…”

Section: Discussionmentioning

confidence: 99%

ARHGAP42 promotes cell migration and invasion involving PI3K/Akt signaling pathway in nasopharyngeal carcinoma

Lin

Ding

et al. 2018

Cancer Medicine

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Rho GTPase‐activating protein 42 was identified as an inhibitor of RhoA to maintain normal blood pressure homeostasis. However, the effect of ARHGAP42 in promoting cell malignancy in nasopharyngeal carcinoma is demonstrated in this study. Microarray and real‐time quantitative PCR were used for a mRNA profiling of ARHGAP42 in nasopharyngeal primary and metastatic carcinoma tissues. Western blot and immunohistochemical staining were used for detecting the expression of ARHGAP42 protein in nasopharyngeal carcinoma tissues and cell lines. The overexpression and silence experiments of ARHGAP42 were performed in NPC cell lines using siRNA and expressive plasmid for evaluating cancer cell migration and invasion in vitro. Real‐time quantitative PCR, western blot, and transwell test were employed for with the function of ARHGAP42 and its antisense lncRNA uc010rul. We confirmed the elevated expression of ARHGAP42 in metastatic NPC tissues of mRNA and protein for the first time. Immunohistochemical analysis indicated that NPC patients with highly ARHGAP42 expression were significantly associated with shorter metastasis‐free survival. Knockdown of ARHGAP42 resulted in significant inhibition of nasopharyngeal cancer cell migration and invasion in vitro, and the overexpression of ARHGAP42 showed the opposite effects. In addition, the silence of uc010rul resulted in ARHGAP42 expression decrease and significant inhibition of nasopharyngeal cancer cell migration and invasion. High expression of ARHGAP42 is associated with poor metastasis‐free survival of nasopharyngeal carcinoma patients. ARHGAP42 promotes migration and invasion of nasopharyngeal carcinoma cells in vitro; the antisense lncRNA may be involved in this effect.

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Section: Discussionmentioning

confidence: 99%

ARHGAP42 promotes cell migration and invasion involving PI3K/Akt signaling pathway in nasopharyngeal carcinoma

Lin

Ding

et al. 2018

Cancer Medicine

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“…This represents a negative feedback loop, in which aHIF inhibits the translation of HIF-1a mRNA after chronic hypoxia (Uchida et al 2004). A 20% of the human genome consists of these naturally occurring antisense transcripts, which regulate gene transcription, RNA splicing, polyadenylation, editing, stability, transport, and translation (Yelin et al 2003, Chen et al 2004, Katayama et al 2005. Importantly, besides acting as a transcription factor for hypoxia-inducible genes, HIF-1a also stabilizes the tumor suppressor gene p53 under early hypoxic conditions (An et al 1998).…”

Section: Introductionmentioning

confidence: 99%

Overexpression of the natural antisense hypoxia-inducible factor-1 transcript is associated with malignant pheochromocytoma/paraganglioma

Span

Rao²,

Ophuis³

et al. 2011

Endocrine Related Cancer

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Paragangliomas (PGLs) have widely different metastastic potentials. Two different types of PGLs can be defined by expression profiling. Cluster 1 PGLs exhibit VHL and/or succinate dehydrogenase (SDH) mutations and a pseudohypoxic phenotype. RET and neurofibromatosis type 1 (NF1) mutations occur in cluster 2 tumors characterized by deregulation of the RAS/RAF/MAP kinase signaling cascade. Sporadic PGLs can exhibit either profile. During sustained hypoxia, a natural antisense transcript of hypoxia-inducible factor 1 (aHIF) is expressed. The role of aHIF in the metastatic potential of PGL has not yet been investigated. The aim was to test the hypothesis that genotype-specific overexpression of aHIF is associated with an increased metastatic potential. Tumor samples were collected from 87 patients with PGL. Quantitative PCR was performed for aHIF, vascular endothelial growth factor (VEGF), aquaporin 3, cytochrome b561, p57Kip2, slit homolog 3, and SDHC. Expression was related to mutation status, benign versus malignant tumors, and metastasis-free survival. We found that both aHIF and VEGF were overexpressed in cluster 1 PGLs and in metastatic tumors. In contrast, slit homolog 3, p57Kip2, cytochrome b561, and SDHC showed overexpression in non-metastatic tumors, whereas no such difference was observed for aquaporin 3. Patients with higher expression levels of aHIF and VEGF had a significantly decreased metastasisfree survival. Higher expression levels of SDHC are correlated with an increased metastasis-free survival. In conclusion, we not only demonstrate a higher expression of VEGF in cluster 1 PGL, fitting a profile of pseudohypoxia and angiogenesis, but also of aHIF. Moreover, overexpression of aHIF and VEGF marks a higher metastatic potential in PGL.

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“…Though lncRNAs exhibit poor sequence conservation and are less expressed than are PCGs, they present the highest specificity with respect to cell type, subcellular compartment, developmental stage and in response to environmental stimuli 11, 20, 21…”

Section: Basic Characteristics and Functions Of Lncrnasmentioning

confidence: 99%

Long non‐coding RNAs in brain tumours: Focus on recent epigenetic findings in glioma

Pop

Enciu

Necula

et al. 2018

J Cellular Molecular Medi

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Glioma biology is a major focus in tumour research, primarily due to the aggressiveness and high mortality rate of its most aggressive form, glioblastoma. Progress in understanding the molecular mechanisms behind poor prognosis of glioblastoma, regardless of treatment approaches, has changed the classification of brain tumours after nearly 100 years of relying on anatomopathological criteria. Expanding knowledge in genetic, epigenetic and translational medicine is also beginning to contribute to further elucidating molecular dysregulation in glioma. Long non‐coding RNAs (lncRNAs) and their main representatives, large intergenic non‐coding RNAs (lincRNAs), have recently been under scrutiny in glioma research, revealing novel mechanisms of pathogenesis and reinforcing others. Among those confirmed was the reactivation of events significant for foetal brain development and neuronal commitment. Novel mechanisms of tumour suppression and activation of stem‐like behaviour in tumour cells have also been examined. Interestingly, these processes involve lncRNAs that are present both during normal brain development and in brain malignancies and their reactivation might be explained by epigenetic mechanisms, which we discuss in detail in the present review. In addition, the review discusses the lncRNAs‐induced changes, as well as epigenetic changes that are consequential for tumour formation, affecting, in turn, the expression of various types of lncRNAs.

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Antisense Transcription in the Mammalian Transcriptome

Cited by 1,522 publications

References 26 publications

ARHGAP42 promotes cell migration and invasion involving PI3K/Akt signaling pathway in nasopharyngeal carcinoma

ARHGAP42 promotes cell migration and invasion involving PI3K/Akt signaling pathway in nasopharyngeal carcinoma

Overexpression of the natural antisense hypoxia-inducible factor-1 transcript is associated with malignant pheochromocytoma/paraganglioma

Long non‐coding RNAs in brain tumours: Focus on recent epigenetic findings in glioma

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