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Non-coding RNAs (ncRNAs) have been defined as a class of RNA molecules transcribed from the genome but not encoding proteins, such as microRNAs, long non-coding RNAs, Circular RNAs, and Piwi-interacting RNAs. Accumulating evidence has recently been revealing that ncRNAs become potential druggable targets for regulation of several small-molecule compounds, based on their complex spatial structures and biological functions in cancer therapy. Thus, in this review, we focus on summarizing some new emerging designing strategies, such as high-throughput screening approach, small-molecule microarray approach, structure-based designing approach, phenotypic screening approach, fragment-based designing approach, and pharmacological validation approach. Based on the above-mentioned approaches, a series of representative small-molecule compounds, including Bisphenol-A, Mitoxantrone and Enoxacin have been demonstrated to modulate or selectively target ncRNAs in different types of human cancers. Collectively, these inspiring findings would provide a clue on developing more novel avenues for pharmacological modulations of ncRNAs with small-molecule drugs for future cancer therapeutics.

Designing strategies of small-molecule compounds for modulating non-coding RNAs in cancer therapy