Abstract MicroRNAs (miRNAs) are central post-transcriptional regulators that shape oncogenic and tumor-suppressive networks through RNA-induced silencing complex (RISC)–mediated repression of target mRNAs. Among these, hsa-miR-107—a member of the miR-16 family encoded within an intron of the PANK1 gene—has emerged as a particularly paradoxical regulator in cancer. Accumulating evidence indicates that miR-107 cannot be classified as a single-function miRNA; instead, it behaves as a context-dependent “molecular switch” whose impact is dictated by tissue-specific target availability, tumor stage, and the surrounding regulatory landscape. This review synthesizes mechanistic and translational data explaining how miR-107 exerts opposing roles as both a tumor suppressor and an oncomiR. In tumor-suppressive contexts, miR-107 integrates into stress-response circuitry via a p53/ PANK1 /miR-107 axis, repressing HIF-1β, impairing HIF-1 complex formation, and reducing VEGF-driven angiogenesis. miR-107 also restricts proliferation and invasion by targeting cell-cycle kinases (e.g., CDK6 and CDK8 ), suppressing NOTCH2 signaling in glioma, and attenuating pro-survival PI3K/AKT signaling indirectly in NSCLC through BDNF repression. Conversely, in aggressive cancers, miR-107 promotes malignancy through “meta-oncogenic” disruption of global miRNA biogenesis by targeting DICER1 , enabling EMT programs via loss of miR-200 family activity. It also activates PI3K/AKT signaling through direct repression of PTEN (notably in bladder cancer) and enhances metastatic behavior in colorectal cancer by co-silencing metastasis suppressors such as DAPK and KLF4. A distinctive layer of complexity is added by miR-107-mediated miRNA–miRNA interaction, exemplified by direct destabilization of the tumor-suppressive let-7 family in advanced breast cancer. Therefore, the review highlights higher-order regulation by lncRNA competing endogenous RNA (ceRNA) “sponges” that sequester miR-107 (e.g., LINC00662, UASR1, H19, MFI2-AS1), thereby rewiring downstream oncogenic pathways. We discuss emerging clinical implications of miR-107 as a biomarker and as a therapeutic lever for reversing multidrug resistance, while outlining key challenges for safe, context-aware miRNA-based interventions.
Ragab et al. (Tue,) studied this question.