[3][4] Dysregulation of let-7 contributes to cancer development in humans by preventing differentiation of cells, leaving them stuck in a stem-cell like state.

[1] In humans, mature let-7 acts via RNA-induced silencing by complexing with RISC and binding to target mRNA, preventing translation into protein.

[8] Soon, let-7 was found in the fruit fly (Drosophila), and identified as the first known human miRNA by a BLAST (basic local alignment search tool) research.

As one of the genes involved in (but not essential for) induced pluripotent stem (iPS) cell reprogramming,[21] LIN28 expression is reciprocal to that of mature let-7.

Furthermore, let-7 could lead to IMP1 (insulin-like growth factor II mRNA-binding protein) depletion, which destabilizes MYC mRNA, thus forming an indirect regulatory pathway.

[32] Let-7 also inhibits several components of DNA replication machinery, transcription factors, even some tumor suppressor genes and checkpoint regulators.

Macrophages stimulated with live bacteria or purified microbial components down-regulate the expression of several members of the let-7 microRNA family to relieve repression of immune-modulatory cytokines IL-6 and IL-10.

[36][37] Let-7 has furthermore been reported to regulate the production of cytokine IL-13 by T lymphocytes during allergic airway inflammation thus linking this microRNA to adaptive immunity as well.

[38] Down-modulation of let-7 negative regulator Lin28b in human T lymphocytes is believed to accrue during early neonate development to reprogram the immune system towards defense.

Numerous reports have shown that the expression levels of let-7 are frequently low and the chromosomal clusters of let-7 are often deleted in many cancers.

[43] Lung cancer, for instance, has several key oncogenic mutations including p53, RAS and MYC, some of which may directly correlate with the reduced expression of let-7, and may be repressed by introduction of let-7.

[41] Intranasal administration of let-7 has already been found effective in reducing tumor growth in a transgenic mouse model of lung cancer.

[44] Similar restoration of let-7 was also shown to inhibit cell proliferation in breast, colon and hepatic cancers, lymphoma, and uterine leiomyoma.