The BRCA1 and BRCA2 Suppressor Genes - Therapeutic Strategies in Cancer Biology and Pathology - page 107

Oestrogen

ERα

miRNA-335 BRCA1 Compensatory

ID ↓

Sox4

Cell migration/invasion

Figure 17.1 Regulatory loops of cell migration/invasion involving miRNA-335, BRCA1 and
ERα. A second regulatory route not involving ERα is also shown. This involves Sox4. Suppression
of Sox4 miRNA-335 would be expected to lead the suppression of cell migration/invasion.

level, but when the endogenous miRNA is suppressed using antisense oligonucle-
otides, ID4 expression increases, possibly a compensatory effect indicating a regu-
latory loop involving miRNA-335, BRCA1 and ERα. BRCA1 expression is said
to inversely relate to both ERα and ID4 ( Roldan et al., 2006), which insinuates a
notion of co-regulatory link involving the miRNA, BRCA1 and ID4, but not ERα.
Here miRNA-335 would be just as effective in suppressing aggressive behaviour of
tumours. Indeed the miRNA does inhibit cell migration and metastasis as assayed
by the less than ideal assay of lung colonisation upon tail vein injection even in the
absence of ER. This in fact seems to occur by a different route, namely by inhibiting
SOX4, an activator of EMT (Zhang et al., 2012c) ( Figure 17.1 ).