Improved cancer inhibition by miR-143 with a longer passenger strand than natural miR-143

• Published in: Biochemical and biophysical research communications 2020-04, Vol.524 (4), p.810-815
• Main Authors: Ida, Hiroyuki, Tanabe, Toshizumi, Tachibana, Akira
• Format: Article
• Language: English
• Subjects: Anti-cancer drug; Chimeric long passenger strand; DNA; G-rich flanking region; Long passenger strand; microRNA; miRNA; neoplasm cells; reporter genes
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2020.02.010

We improved miR-143, which inhibits the growth of cancer cells, by the replacement of the passenger strand. As a result, new miR-143 variants were developed with a single mismatch at the 4th position from the 3′-terminal of the guide strand and an RNA passenger strand with a G-rich flanking DNA region. A reporter gene assay showed that the 80% inhibitory concentration of the new miR-143, long miR-143, was 69 pM, which was three times lower than that of natural miR-143. Long miR-143 inhibited the growth of two cancer cell lines, HeLa–S3 and MIAPaCa-2, more effectively than natural miR-143. This method could be applied to other miRNA families and should be useful for the development of miRNA drugs. [Display omitted] •We improved miR-143 by the replacement of the passenger strand.•A single mismatch near the 3′-terminal of the guide strand enhanced miRNA activity.•An RNA passenger strand with a G-rich flanking DNA region also enhanced.•Improved “long miR-143” showed more than 3 times the activity of natural miR-143.•Long miR-143 inhibited the cancer cell growth more effectively than natural miR-143.