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. 2012 Oct 24;122(11):4003–4011. doi: 10.1172/JCI65171

Figure 5. Blocking potential mutation sites decreases extravillous trophoblast invasion.

Figure 5

(A) 3 potential mutations were investigated in detail. RW18-5 (C→T at position 101,120,459) occurred in family 9401; the mutation on the other allele has not yet been identified. HAPLO378 (A→G at position 101,319,702) and HAPLO215Rev (G→C at position 101,241,930) occurred as compound heterozygous mutations in family 9265. HAPLO378 was also present in family 93113. Women affected by HELLP are indicated by black symbols; children born of HELLP pregnancies are indicated by gray symbols. Potential mutagenic alleles are also shaded gray. (B) Morpholinos at a concentration of 5 μM blocking the potential mutagenic sites upregulated expression of the HELLP lincRNA in SGHPL-5 cells. (C) Upregulation of the HELLP lincRNA led to upregulation of downstream effector genes that showed downregulation after siRNA-mediated knockdown of the transcript when the RW18-5 or HAPLO215Rev morpholino was used at a concentration of 5 μM. The combination of HAPLO378 and HAPLO215Rev (2.5 μM each) also upregulated the downstream effector genes. (D) Invasion of SGHPL-5 cells significantly decreased when RW18-5 morpholinos were introduced, whereas HAPLO215Rev trended toward a significant decrease in invasion. HAPLO378 did not affect invasion. The combination of HAPLO215Rev and HAPLO378 (2.5 μM each) significantly decreased the amount of invaded cells. *P < 0.05; **P < 0.01.