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Long non-coding RNAs in cancer and development: where do we go from here?

Haemmerle M, Gutschner T - Int J Mol Sci (2015)

Bottom Line: Consequently, deregulation of lncRNA expression contributes to carcinogenesis and is associated with human diseases, e.g., neurodegenerative disorders like Alzheimer's Disease.We will delineate strategies for lncRNA gene targeting in vivo, and we will briefly discuss important consideration and pitfalls when investigating lncRNA functions in knockout animal models.Finally, we will highlight future opportunities for lncRNAs research by applying the concept of cross-species comparison, which might contribute to novel disease biomarker discovery and might identify lncRNAs as potential therapeutic targets.

View Article: PubMed Central - PubMed

Affiliation: Department of Gynecologic Oncology and Reproductive Medicine, the University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA. mhaemmerle@mdanderson.org.

ABSTRACT
Recent genome-wide expression profiling studies have uncovered a huge amount of novel, long non-protein-coding RNA transcripts (lncRNA). In general, these transcripts possess a low, but tissue-specific expression, and their nucleotide sequences are often poorly conserved. However, several studies showed that lncRNAs can have important roles for normal tissue development and regulate cellular pluripotency as well as differentiation. Moreover, lncRNAs are implicated in the control of multiple molecular pathways leading to gene expression changes and thus, ultimately modulate cell proliferation, migration and apoptosis. Consequently, deregulation of lncRNA expression contributes to carcinogenesis and is associated with human diseases, e.g., neurodegenerative disorders like Alzheimer's Disease. Here, we will focus on some major challenges of lncRNA research, especially loss-of-function studies. We will delineate strategies for lncRNA gene targeting in vivo, and we will briefly discuss important consideration and pitfalls when investigating lncRNA functions in knockout animal models. Finally, we will highlight future opportunities for lncRNAs research by applying the concept of cross-species comparison, which might contribute to novel disease biomarker discovery and might identify lncRNAs as potential therapeutic targets.

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Related in: MedlinePlus

Long non-protein-coding RNA (LncRNA) targeting strategies for in vivo loss-of-function studies.
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ijms-16-01395-f001: Long non-protein-coding RNA (LncRNA) targeting strategies for in vivo loss-of-function studies.

Mentions: Several targeting strategies can be used for knocking out protein-coding genes: exon replacements, in frame stop-codon insertion or introduction of insertions that lead to a frame shift, as well as whole gene excisions, truncations or (point) mutations of functional domains. Most of these manipulations need active translation of the RNA transcript to achieve the disruptive effect, and thus are not feasible for lncRNAs. Hence, lncRNA targeting strategies must prevent the whole transcript from being made (Figure 1).


Long non-coding RNAs in cancer and development: where do we go from here?

Haemmerle M, Gutschner T - Int J Mol Sci (2015)

Long non-protein-coding RNA (LncRNA) targeting strategies for in vivo loss-of-function studies.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4307309&req=5

ijms-16-01395-f001: Long non-protein-coding RNA (LncRNA) targeting strategies for in vivo loss-of-function studies.
Mentions: Several targeting strategies can be used for knocking out protein-coding genes: exon replacements, in frame stop-codon insertion or introduction of insertions that lead to a frame shift, as well as whole gene excisions, truncations or (point) mutations of functional domains. Most of these manipulations need active translation of the RNA transcript to achieve the disruptive effect, and thus are not feasible for lncRNAs. Hence, lncRNA targeting strategies must prevent the whole transcript from being made (Figure 1).

Bottom Line: Consequently, deregulation of lncRNA expression contributes to carcinogenesis and is associated with human diseases, e.g., neurodegenerative disorders like Alzheimer's Disease.We will delineate strategies for lncRNA gene targeting in vivo, and we will briefly discuss important consideration and pitfalls when investigating lncRNA functions in knockout animal models.Finally, we will highlight future opportunities for lncRNAs research by applying the concept of cross-species comparison, which might contribute to novel disease biomarker discovery and might identify lncRNAs as potential therapeutic targets.

View Article: PubMed Central - PubMed

Affiliation: Department of Gynecologic Oncology and Reproductive Medicine, the University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA. mhaemmerle@mdanderson.org.

ABSTRACT
Recent genome-wide expression profiling studies have uncovered a huge amount of novel, long non-protein-coding RNA transcripts (lncRNA). In general, these transcripts possess a low, but tissue-specific expression, and their nucleotide sequences are often poorly conserved. However, several studies showed that lncRNAs can have important roles for normal tissue development and regulate cellular pluripotency as well as differentiation. Moreover, lncRNAs are implicated in the control of multiple molecular pathways leading to gene expression changes and thus, ultimately modulate cell proliferation, migration and apoptosis. Consequently, deregulation of lncRNA expression contributes to carcinogenesis and is associated with human diseases, e.g., neurodegenerative disorders like Alzheimer's Disease. Here, we will focus on some major challenges of lncRNA research, especially loss-of-function studies. We will delineate strategies for lncRNA gene targeting in vivo, and we will briefly discuss important consideration and pitfalls when investigating lncRNA functions in knockout animal models. Finally, we will highlight future opportunities for lncRNAs research by applying the concept of cross-species comparison, which might contribute to novel disease biomarker discovery and might identify lncRNAs as potential therapeutic targets.

Show MeSH
Related in: MedlinePlus