Fig 3.

Identifying gained/lost indirect cePathway relationships (a). In normal when regulating miRNAs (R1 and R2) are active (in abundance relative to other competing molecules[21]), down-regulation of x would direct more copies of R1 to repress y. In turn, repressed y would direct R2 to repress z. Overall, ceRNA relationship on (x, y) and (y, z) would yield indirect ceRNA relationship on (x, z). In tumor when (x, y) lost ceRNA relationship possibly in association to inactivation of the regulating miRNAs, down-regulation of x would not repress y and z, representing the loss of not only direct ceRNA relationship in (x, y) and (y, z) but also indirect ceRNA relationship in (x, z). From normal and tumor condition, (x, z) would lose co-expression in tumors (Δρ<0) altogether with (y, z) and (x, z). (b). Accumulative distribution of co-expression (ρ) in direct and indirect ceRNA relationships (found in direct and indirect cePathway relationships) in normal samples, compared to the same number of random pairs (n = 5,000).