Sip1/tuftelin-interacting protein (STIP), a multidomain nuclear protein, is a novel factor associated with the spliceosome, yet its role and molecular function in cancer remain unknown. In this study, we show, for the first time, that STIP is overexpressed in non-small cell lung cancer (NSCLC) tissues compared to adjacent normal lung tissues. The depletion of endogenous STIP inhibited NSCLC cell proliferation in vitro and in vivo, caused cell cycle arrest and induced apoptosis. Cell cycle arrest at the G2/M phase was associated with the expression and activity of the cyclin B1-CDK1 (cyclin-dependent kinase 1) complex. We also provide evidence that STIP knockdown induced apoptosis by activating both caspase-9 and caspase-3 and by altering the Bcl-2/Bax expression ratio. RNA sequencing data indicated that the MAPK mitogen-activated protein kinases, Wnt, PI3K/AKT, and NF-kappa B (nuclear factor kappa-light-chain-enhancer of activated B cells) signalling pathways might be involved in STIP-mediated tumour regulation. Collectively, these results suggest that STIP may be a novel potential diagnostic and therapeutic target for NSCLC.
[1]Hunan Univ, Collaborat Innovat Ctr Mol Engn Theranost, State Key Lab Chemo Biosensing & Chemometr, Mol Sci & Biomed Lab,Coll Biol,Coll Chem & Chem E, Changsha 410082, Hunan, Peoples R China.
[2]Kunming Med Univ, Tumour Hosp Yunnan Prov, Canc Biotherapy Ctr, Kunming, Yunnan, Peoples R China.
[3]Cent S Univ, State Key Lab Med Genet, Sch Life Sci, Changsha, Hunan, Peoples R China.
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