Regulatory roles of tumor‐suppressor proteins and noncoding RNA in cancer and normal cell functions

Garen, Alan; Xu, Shumin

doi:10.1002/ijc.23285

Cited by 23 publications

(28 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The function of this long ncRNA is not known. Its abundance and aberrant expression in many cancers suggests that it plays a pivotal role in the development of cancer (20).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

MALAT-1: A long non-coding RNA and its important 3' end functional motif in colorectal cancer metastasis

Yang²,

Tian³

et al. 2011

Int J Oncol

167

110

View full text Add to dashboard Cite

Abstract. The human metastasis associated lung adenocarcinoma transcript 1 (MALAT-1) as a long non-coding RNA known to be misregulated in many people who are detected with cancer. Our earlier studies found that MALAT-1 plays a pivotal role in colorectal cancer (CRC) metastasis. In this study, we analyzed the MALAT-1 gene in five fragments. We employed the sequencing process to identify MALAT-1 mutations in the following types of samples: CRC cells (SW620, SW480), normal colorectal tissues, and primary CRC tissues. We were successful in detecting the following mutations: fragment 5434 nt-6951 nt of the MALAT-1 was mutated in SW620 cells, while fragments 5434 nt-6951 nt and 6918 nt-8441 nt of MALAT-1 were mutated in SW480 cancer cells and primary CRC tissues. We over-expressed five fragments of MALAT-1 in the CRC cell line SW480; simultaneously ensuring that MALAT-1 had low expression. Our data illustrated that one of the 5 fragments (6918 nt-8441 nt) located at the 3' end of MALAT-1 plays a pivotal role in the biological processes of cell proliferation, migration and invasion. Based on these observations, we can infer that the 3' end of MALAT-1 is an important biological motif in the invasion and metastasis of CRC cells. We have successfully presented the first evidence that mutations were found on the long non-coding RNA MALAT-1 in CRC. Moreover, long non-coding RNA MALAT-1 has an important biological motif located at the 3' end of MALAT-1 (6918 nt-8441 nt) in CRC. Our study gives a new direction to research primarily focused on exploring the molecular mechanisms occurring during the invasion and metastasis of CRC.

show abstract

“…The function of this long ncRNA is not known. Its abundance and aberrant expression in many cancers suggests that it plays a pivotal role in the development of cancer (20).…”

Section: Discussionmentioning

confidence: 99%

“…Third, it has been identified as a regulator of tumor suppressor proteins (e.g. PTB-associated splicing factor (PSF) (20). In recent studies, a highly conserved tRNA-like small RNA of 61 nucleotides, originating from the MALAT-1 locus (7519 nt to 7576 nt), was found exclusively in the cytoplasm.…”

Section: Discussionmentioning

confidence: 99%

MALAT-1: A long non-coding RNA and its important 3' end functional motif in colorectal cancer metastasis

Yang²,

Tian³

et al. 2011

Int J Oncol

167

110

View full text Add to dashboard Cite

show abstract

“…Related studies described a mechanism for reversible regulation of proto-oncogene transcription, involving the protein hPSF that binds to the regulatory region of a proto-oncogene and represses transcription, and VL30-1 RNA, a mouse noncoding retroelement RNA, that binds to hPSF, forming a hPSF/RNA complex that dissociates from a proto-oncogene, activating transcription (2)(3)(4)(5). Because VL30-1 RNA is not encoded in the human genome (7), we screened by affinity chromatography a library of RNA fragments, derived from the RNA of a human tumor cell nucleus, for RNAs that bind to hPSF.…”

Section: Discussionmentioning

confidence: 99%

“…The finding that VL30-1 RNA, a mouse retroelement RNA that is not encoded in the human genome, binds selectively to hPSF protein and reverses repression of proto-oncogene transcription (2)(3)(4)(5), prompted a search for human RNAs that have a similar function as VL30-1 RNA. The procedure involved synthesizing a library of RNA fragments from the nuclear RNA repertoire of a human melanoma line and selecting by affinity chromatography RNA fragments that bind to hPSF.…”

Section: Cloning and Mapping Human Rna Fragments That Bind To Hpsfmentioning

confidence: 99%

“…T he protein PSF (1) contains a DNA-binding domain (DBD) that binds to the regulatory region of a proto-oncogene and represses transcription, and 2 RNA-binding domains (RBDs) that bind VL30-1 RNA, releasing PSF from a repressed protooncogene and activating transcription (2)(3)(4)(5). Mouse and human genomes encode homologous PSF proteins with Ϸ95% sequence identity, whereas the VL30-1 gene belongs to a family of mouse noncoding retroelement genes (6) that is not present in the human genome (7).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Role of human noncoding RNAs in the control of tumorigenesis

Feng

Lian

et al. 2009

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

Self Cite

169

136

View full text Add to dashboard Cite

Related studies showed that the protein PSF represses protooncogene transcription, and VL30 -1 RNA, a mouse noncoding retroelement RNA, binds and releases PSF from a proto-oncogene, activating transcription. Here we show that this mechanism regulates tumorigenesis in human cells, with human RNAs replacing VL30 -1 RNA. A library of human RNA fragments was used to isolate, by affinity chromatography, 5 noncoding RNA fragments that bind to human PSF (hPSF), releasing hPSF from a protooncogene and activating transcription. T he protein PSF (1) contains a DNA-binding domain (DBD) that binds to the regulatory region of a proto-oncogene and represses transcription, and 2 RNA-binding domains (RBDs) that bind VL30-1 RNA, releasing PSF from a repressed protooncogene and activating transcription (2-5). Mouse and human genomes encode homologous PSF proteins with Ϸ95% sequence identity, whereas the VL30-1 gene belongs to a family of mouse noncoding retroelement genes (6) that is not present in the human genome (7). To determine whether the PSF/RNA regulatory mechanism functions in human cells, a library of RNA fragments was constructed from the nuclear RNA repertoire of a human tumor cell, and the library was screened by affinity chromatography for RNAs that bind to human PSF (hPSF). The screen identified 5 hPSF-binding noncoding RNA fragments that release hPSF from a repressed proto-oncogene and activate transcription, similar to VL30-1 RNA. Each human RNA fragment maps to a matching sequence in a different human gene. The following experiments show that human hPSF-binding RNAs are involved in the control of tumorigenesis. Results Cloning and Mapping Human RNA Fragments That Bind to hPSFProtein. The finding that VL30-1 RNA, a mouse retroelement RNA that is not encoded in the human genome, binds selectively to hPSF protein and reverses repression of proto-oncogene transcription (2-5), prompted a search for human RNAs that have a similar function as VL30-1 RNA. The procedure involved synthesizing a library of RNA fragments from the nuclear RNA repertoire of a human melanoma line and selecting by affinity chromatography RNA fragments that bind to hPSF. The procedure yielded 5 such RNA fragments, 4 of which were mapped, by sequence identity, within 1 of the following genes: L1PA16, a non-LTR retroelement gene (8); MER11C, a LTR retroelement gene (9); MALAT-1, a noncoding gene (10, 11); or HN, a mitochondrial gene coding for the peptide humanin (12); a fifth fragment, not shown in the figure, maps to a region that has not been characterized ( Fig. 1 and SI Text).The sequence of the HN RNA fragment is 100% identical to a sequence in the mitochondrial 16S ribosomal RNA gene and is 85% identical to positions 21947595-21947823 on nuclear chromosome 17. Further testing showed that the HN RNA fragment is derived from the mitochondrial HN RNA and not from the nuclear RNA (SI Text). The mitochondrial HN RNA might be translocated to the nucleus or derived from a mitochondrial contamination in the nuclear preparation.Release of hPSF from ...

show abstract

Environmental influence on L1 retrotransposons in the adult hippocampus

et al. 2009

View full text Add to dashboard Cite

It is well established that neuronal circuits can be shaped by experience. Neuronal plasticity can be achieved by synaptic competitive interactions and the addition of new neuronal units in neurogenic regions of the adult brain. Recent data have suggested that neuronal progenitor cells can accommodate somatic LINE-1 (Long Interspersed Nuclear Elements-1 or L1) retrotransposition. Genomic L1 insertions may up-or down-regulate transcriptional control of gene expression. Here, we show that exercise has a positive effect on a L1-EGFP reporter in vivo. We found that neurons from mice that experience voluntary exercise are more likely to activate an EGFP reporter marker, representing L1 insertions in the brain, when compared with sedentary animals. In the hippocampus, a neurogenic region of the adult brain, EGFP expression is mainly found in cells localized in the subgranular layer of the dentate gyrus. This observation implies that neuronal progenitor cells may support de novo retrotransposition upon exposure to a new environment. Such evidence suggests that experience-dependent L1 retrotransposition may contribute to the physiological consequences of neuronal plasticity.

show abstract

Regulatory roles of tumor‐suppressor proteins and noncoding RNA in cancer and normal cell functions

Cited by 23 publications

References 43 publications

MALAT-1: A long non-coding RNA and its important 3' end functional motif in colorectal cancer metastasis

MALAT-1: A long non-coding RNA and its important 3' end functional motif in colorectal cancer metastasis

Role of human noncoding RNAs in the control of tumorigenesis

Environmental influence on L1 retrotransposons in the adult hippocampus

Contact Info

Product

Resources

About