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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,mes-senger 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 per-sonalized therapeutics.