MicroRNA-135 family (miR-135)

The MicroRNA-135 family, primarily consisting of miR-135a and miR-135b, represents a group of small non-coding RNAs that play a critical role in post-transcriptional gene regulation. miR-135b is frequently characterized as an oncomiR because it is significantly upregulated in various malignancies, including colorectal and breast cancers, where it promotes tumor progression by targeting tumor suppressor genes such as Adenomatous Polyposis Coli (APC) and FOXO1 (PMID: 23934151, 25103499). Because miR-135b shares a nearly identical seed sequence with miR-135a—differing by only a single internal nucleotide—therapeutic strategies must account for the high degree of sequence similarity within the family. Drugs targeting these microRNAs, such as antisense antagomirs or locked nucleic acids (LNAs), aim to inhibit their function to restore normal cellular signaling, particularly the Wnt/beta-catenin pathway. However, the 'partial sequence similarity' mentioned in the target name highlights a major pharmacological challenge: ensuring specificity to avoid off-target effects on other microRNAs that share the same seed region or high sequence homology (miRBase, 2023). Clinical development of miR-135 inhibitors is ongoing in preclinical models, focusing on improving delivery mechanisms and minimizing systemic toxicity.

Other names

miR-135amiR-135bhsa-mir-135a-1hsa-mir-135a-2hsa-mir-135bMicroRNA 135b

Antisense oligonucleotides (antagomirs) bind with high affinity to the mature microRNA sequence, sterically blocking its ability to incorporate into the RNA-induced silencing complex (RISC) or preventing its binding to target mRNA 3' UTRs, thereby restoring the expression of suppressed tumor suppressor genes.