Non-coding RNAs: the new central dogma of cancer biology
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n-coding RNAs: the new central dogma of cancer biology 1
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Phei Er Saw , Xiaoding Xu , Jianing Chen & Er-Wei Song 1
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Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; 2 Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China Received June 13, 2020; accepted July 27, 2020; published online September 11, 2020
The central dogma of molecular biology states that the functions of RNA revolve around protein translation. Until the last decade, most researches were geared towards characterization of RNAs as intermediaries in protein translation, namely, messenger RNAs (mRNAs) as temporary copies of genetic information, ribosomal RNAs (rRNAs) as a main component of ribosome, or translators of codon sequence (tRNAs). The statistical reality, however, is that these processes account for less than 2% of the genome, and insufficiently explain the functionality of 98% of transcribed RNAs. Recent discoveries have unveiled thousands of unique non-coding RNAs (ncRNAs) and shifted the perception of them from being “junk” transcriptional products to “yet to be elucidated”—and potentially monumentally important—RNAs. Most ncRNAs are now known as key regulators in various networks in which they could lead to specific cellular responses and fates. In major cancers, ncRNAs have been identified as both oncogenic drivers and tumor suppressors, indicating a complex regulatory network among these ncRNAs. Herein, we provide a comprehensive review of the various ncRNAs and their functional roles in cancer, and the pre-clinical and clinical development of ncRNA-based therapeutics. A deeper understanding of ncRNAs could facilitate better design of personalized therapeutics. non-coding RNAs, anti-cancer therapeutics, personalized intervention, miRNA, lncRNA, circRNA Citation:
Saw, P.E., Xu, X., Chen, J., and Song, E.W. (2020). Non-coding RNAs: the new central dogma of cancer biology. Sci China Life Sci 63, https://doi. org/10.1007/s11427-020-1700-9
Introduction For a long time prior to the proposition of the biological “central dogma”, ncRNAs were commonly considered to be mere intermediary products, possessing no function. Nevertheless, recent breakthroughs in sequencing technology, namely ENCODE and FANTOM, have enabled the characterization of functional genomic elements on a larger scale, triggering a substantial paradigm shift in the field of cancer biology (Carninci et al., 2005; Katayama et al., 2005; Birney et al., 2007; Wang et al., 2020). The findings suggest that an enormous amount of non-coding RNAs are also transcribed, including microRNAs (miRNA; all abbrevia*Corresponding author (email: [email protected])
tions are listed in Table S1 in Supporting Information), circular RNAs (circRNAs), and long non-coding RNAs (lncRNAs), amongst others. Recently, a new class of noncoding RNA has emerged (i.e., small nuclear RNAs, snRNAs; piwi-interacting RNAs, piRNAs and
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