1. Nat. Rev. Gastroenterol. Hepatol. doi:10.1038/nrgastro.2017.169
Figure 1 Milestones of non-coding RNA discovery and their roles in hepatocellular carcinoma
Figure 1 | Milestones of non-coding RNA discovery and their roles in hepatocellular carcinoma. RNAs were viewed as templates (mRNAs) and infrastructural platforms (tRNAs and ribosomal RNAs (rRNAs)) for protein translation, as stated in the central dogma of biology proposed by Francis Crick in 1958 (REF. 5). Discovery of heterogenous nuclear RNA (hnRNAs) in complex organisms suggested that RNA has additional roles185. In the 1970s, non-coding regions in precursor mRNAs were defined as introns186, and it was later discovered that small nuclear RNAs (snRNAs) were critically involved in RNA splicing187. In the 1990s, another class of small non-coding RNAs (ncRNAs), small nucleolar RNA (snoRNA), was shown to guide chemical modification of rRNAs, tRNAs and snRNAs188. In 1993, a seminal publication by Lee et al. reported the discovery in Caenorhabditis elegans of lin‑4, the first identified microRNA (miRNA), marking an important breakthrough189. Later, important components of the RNA interference (RNAi) machinery were uncovered190–192. The research of miRNA has exponentially expanded since The first miRNA expression profiling study in human hepatocellular carcinoma (HCC) was conducted by Murakami et al. in 2006 (REF. 13). Concurrent to the discovery of miRNAs, longer RNAs such as H19 and Xist were found to be non-protein coding193,194. In 2007, the long ncRNA (lncRNA) HOTAIR was discovered and shown to epigenetically regulate genes in a polycomb repressive complex 2 (PRC2)‑dependent manner50. HULC was the first lncRNA identified as overexpressed in HCC43. Thereafter, the first lncRNA expression profiling study in HCC was conducted by Yang et al. in 2011 (REF. 160). AGO, Argonaute; circRNA, circular RNA; Dicer, endoribonuclease Dicer; Drosha, RNase 3; ENCODE, Encyclopaedia of DNA Elements; eRNAs, enhancer RNAs; piRNA, PIWI-interacting RNA.
Wong, C.-M. et al. (2018) Non-coding RNAs in hepatocellular carcinoma: molecular functions and pathological implications
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