High Throughput FISH Screening Identifies Small Molecules That Modulate Oncogenic lncRNA MALAT1 via GSK3B and hnRNPs.

Interestingly, in comparison to GSK3B knockdown, we found a partial but highly significant prevention of Niclosamide or Tyrphostin 9 induced reduction of nuclear MALAT1 levels after the knockdown of hnRNPC and hnRNPK and partially significant effects for the knockdown of AUF1 ( Figure 6 B). hnRNPs have been reported to require N6-methyladenosine (m6A) RNA modification to enable MALAT1 binding [ 13 , 35 , 36 ], however, we found no strong effect of METTL16 knockdown, a m6A writer known to interact with MALAT1 [ 39 ], on MALAT1 nuclear levels ( Figure 6 B).

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Of the six tested hits, four showed highly significant effects on nuclear MALAT1 levels at 10 μM and 2 h incubation compared with showing no effects on the pre-fixed cells ( Figure 3 A,B and Supplemental Figure S3 ).

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