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Long non-coding RNAs (long ncRNAs, lncRNAs) are a large class of RNA molecules with a length of >200 nucleotides that are not translated into protein. LncRNAs are widely expressed in human genome. They are mainly transcribed by RNA polymerase II (Pol II). Statistics suggest that the human genome contains more than 16,000 or maybe 100000 lncRNA genes. The typical structure of a lncRNA is often capped by 7-methyl guanosine (m7G) at the 5′ end, polyadenylated at the 3′ end and spliced similarly to mRNAs. The function of lncRNAs can also be discovered by their exogenous overexpression, knockdown or knockout. Studies accumulated over the last decades have shown that lncRNAs play key roles in gene regulation, various cellular activities and diseases. Therapeutic targeting of lncRNAs has become an attractive approach for the treatment of cancers as well as many other diseases. For example, antisense oligonucleotides (ASOs) which are single-stranded DNA oligos that can be used for downregulating lncRNAs.

References

[1] Statello, L., Guo, CJ., Chen, LL. et al. Gene regulation by long non-coding RNAs and its biological functions. Nat Rev Mol Cell Biol 22, 96–118 (2021).
[2] Zhu Y, Liu Q, Liao M, Diao L, Wu T, Liao W, Wang Z, Li B, Zhang S, Wang S, Xie W, Jiang Y, Xu N, Zeng Y, Yang BB, Zhang Y. Overexpression of lncRNA EPB41L4A-AS1 Induces Metabolic Reprogramming in Trophoblast Cells and Placenta Tissue of Miscarriage. Mol Ther Nucleic Acids. 2019 Dec 6;18:518-532.
[3] Chen L, Yang H, Xiao Y, Tang X, Li Y, Han Q, Fu J, Yang Y, Zhu Y. Lentiviral-mediated overexpression of long non-coding RNA GAS5 reduces invasion by mediating MMP2 expression and activity in human melanoma cells. Int J Oncol. 2016 Apr;48(4):1509-18.
[4] Liu SJ, Lim DA. Modulating the expression of long non-coding RNAs for functional studies. EMBO Rep. 2018 Dec;19(12):e46955.
[5] Ren XY, Yang WB, Tian Y. Overexpression of long noncoding RNA PTPRG-AS1 is associated with poor prognosis in epithelial ovarian cancer. Rev Assoc Med Bras (1992). 2020 Jul;66(7):948-953.
[6] Wang Y, Wang K, Zhang L, Tan Y, Hu Z, Dang L, Zhou H, Li G, Wang H, Zhang S, Shi F, Cao X, Zhang G. Targeted overexpression of the long noncoding RNA ODSM can regulate osteoblast function in vitro and in vivo. Cell Death Dis. 2020 Feb 18;11(2):133.
[7] Zhang Y, Huang YX, Jin X, Chen J, Peng L, Wang DL, Li Y, Yao XY, Liao JY, He JH, Hu K, Lu D, Guo Y, Yin D. Overexpression of lncRNAs with endogenous lengths and functions using a lncRNA delivery system based on transposon. J Nanobiotechnology. 2021 Oct 2;19(1):303.

 

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