INTS3, also known as Integrator subunit 3, is a crucial component of the integrator complex. It plays diverse essential functions, being involved in DNA damage repair pathways, homologous recombination-dependent repair of double-strand breaks (DSBs), and ataxia-telangiectasia mutated (ATM)-dependent signaling pathways. It also impacts RNA polymerase II (RNAPII) transcription termination and is related to RNA-binding protein functions, which are vital for maintaining genome stability and cell survival [2,4].

In acute myeloid leukaemia, IDH2 and SRSF2 double-mutant cells show aberrant splicing and reduced expression of INTS3, along with increased RNAPII stalling. Aberrant INTS3 splicing, in concert with mutant IDH2 and dependent on mutant SRSF2, contributes to leukaemogenesis [1].

In colorectal cancer, deletion/depletion of INTS3 triggers apoptosis, and in vitro experiments and RNA sequencing show it destabilizes pro-apoptotic gene transcripts, supporting CRC cell survival [3].

In conclusion, INTS3 has multifaceted functions in DNA damage repair, transcription termination, and cell survival-related processes. Its role in diseases like leukaemia and colorectal cancer, as revealed through functional studies, highlights its significance in understanding disease mechanisms. The study of INTS3 knockout or conditional knockout models in these disease areas can potentially provide more insights into its functions and offer new therapeutic strategies.