MBNL1 alternative splicing isoforms play opposing roles in cancer

Abstract

MBNL1 proteins lacking exon 7 (−ex7) are antisurvival factors with tumor suppressive role that cancer cells tend to down-regulate in favor of MBNL +ex7 isoforms.

The SRSF3-MBNL1-Acin1 circuit constitutes an emerging axis to lessen DNA fragmentation in colorectal cancer via an alternative splicing mechanism

“…The MBNL1 Δex7 isoform was reported to cause DNA damage, which diminished carcinogenic signatures, including cell viability [24] . Among apoptosis-related factors, apoptotic chromatin condensation inducer 1 (also referred as Acin1; NC_000014) was multifunctionally involved in caspase-3-induced chromatin condensation and splicing regulation with SAP18 and RNPS1, which was termed the apoptosis and splicing-associated protein (ASAP) [34 , 35] .…”

“…MBNL1 was demonstrated to be a master splicing regulator for shaping transcriptomic profiles throughout the development of striated muscle and blood lineages [42 , 43] . Even though the tumor-suppressive influence of MBNL1 toward cancer cells via AS regulation was recently revealed [23] , the MBNL1 isoform was reported to exert an opposite effect on carcinogenic signatures [24] . The presence of the MBNL1 isoform lacking exon 7 was shown to cause DNA damage, which in turn interfered with cell viability and migration [24] .…”

“…Even though the tumor-suppressive influence of MBNL1 toward cancer cells via AS regulation was recently revealed [23] , the MBNL1 isoform was reported to exert an opposite effect on carcinogenic signatures [24] . The presence of the MBNL1 isoform lacking exon 7 was shown to cause DNA damage, which in turn interfered with cell viability and migration [24] . In this study, relatively high levels of exon 5- and exon 7-included MBNL1 8 transcripts were identified in cancerous tissues and derived cells using different approaches.…”

“…In addition to the molecular mechanism involved in regulating MBNL1 and MBNL1-mediated impacts on tissue development, its influence on carcinogenesis was recently investigated. MBNL1 exerted potential effect on suppressing the progression of breast cancer and CRC possibly through AS regulation [22] , [23] , [24] .…”

A tumor-associated splice-isoform of MAP2K7 drives dedifferentiation in MBNL1-low cancers via JNK activation

“…This isoform is distinct from that described in ref. 17. The specific function of exon5 + MBNL1 isoform in cancer is a current subject of research in our laboratory.…”