Several of the thousands of long noncoding RNAs (lncRNAs) have been functionally characterized in various tumors. In this study, we aimed to explore the function and possible molecular mechanism of lncRNA KTN1 antisense RNA 1 (KTN1-AS1) involved in non-small cell lung cancer (NSCLC). We identified a novel NSCLC-related lncRNA, KTN1 antisense RNA 1 (KTN1-AS1) which was demonstrated to be distinctly highly expressed in NSCLC. KTN1-AS1 upregulation was induced by STAT1. Clinical study also suggested that higher levels of KTN1-AS1 were associated with advanced clinical progression and a shorter five-year overall survival. Functionally, lossof-function assays with in vitro and in vivo experiments revealed that KTN1-AS1 promoted the proliferation, migration, invasion and EMT progress of NSCLC cells, and suppressed apoptosis. Mechanistic studies indicated that miR-23b was a direct target of KTN1-AS1, which functioned as a ceRNA to subsequently facilitate miR-23b's target gene DEPDC1 expression in NSCLC cells. Rescue experiments confirmed that KTN1-AS1 overexpression could increase the colony formation and migration ability suppressed by miR-23b upregulation in NSCLC cells. Overall, our findings imply that STAT1-induced upregulation of KTN1-AS1 display tumor-promotive roles in NSCLC progression via regulating miR-23b/DEPDC1 axis, suggesting that KTN1-AS1 may be a novel biomarker and therapeutic target for NSCLC patients.

An enhanced anti-apoptotic capacity of tumor cells plays an important role in the process of breakpoint cluster region/Abelson tyrosine kinase gene (BCR/ABL)-independent imatinib resistance. We have previously demonstrated that brain expressed X-linked 1 (BEX1) was silenced in secondary imatinib-resistant K562 cells and that re-expression of BEX1 can restore imatinib sensitivity resulting in the induction of apoptosis. However, the mechanism by which BEX1 executes its pro-apoptotic function remains unknown. We identified B-cell lymphoma 2 (BCL-2) as a BEX1-interacting protein using a yeast two-hybrid screen. The interaction between BEX1 and BCL-2 was subsequently confirmed by co-immunoprecipitation assays. Like BCL-2, BEX1 was localized to the mitochondria. The region between 33K and 64Q on BEX1 is important for its localization to the mitochondria and its ability to interact with BCL-2. Additionally, we found that this region is essential for BEX1-regulated imatinib-induced apoptosis. Furthermore, we demonstrated that the interaction between BCL-2 and BEX1 promotes imatinib-induced apoptosis by suppressing the formation of anti-apoptotic BCL-2/BCL-2-associated X protein (BAX) heterodimers. Our results revealed an interaction between BEX1 and BCL-2 and a novel mechanism of imatinib resistance mediated by the BEX1/BCL-2 pathway.

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The brain expressed x‑linked gene 1 (BEX1) is a member of the BEX family and is aberrantly expressed in many cancers. However, the clinical significance of BEX1 expression level and its role in the pathology of esophageal squamous cell cancer (ESCC) remain unknown. In the present study, we determined BEX1 expression in the tumor and adjacent normal tissues from 118 ESCC patients by immunohistochemistry and determined the proliferation and growth of ESCC cells following ectopic overexpression of BEX1 in cultured cells and in mouse‑ESCC xenografts. We observed that BEX1 was downregulated in ESCC tissues compared to adjacent normal tissues, and low BEX1 expression was significantly associated with larger ESCC tumor volume (P<0.001), advanced T stage (P=0.011) and advanced clinical stage (P=0.039). Additionally, survival analysis revealed that low expression of BEX1 significantly predicted poor prognosis in patients with ESCC (P<0.001). Multivariate analysis revealed that low BEX1 expression was an independent prognostic factor of poor survival (P=0.039). In vitro analysis revealed that overexpression of BEX1 inhibited ESCC cell proliferation and colony formation. Furthermore, in vivo tumorigenesis assays revealed that ectopic overexpression of BEX1 suppressed ESCC tumor growth in mice. Further immunoblotting analysis demonstrated that BEX1 upregulation led to reduced expression and phosphorylation of NF‑κB p65, indicating inhibition of the NF‑κB signaling pathway by BEX1. Our findings indicated that low BEX1 expression may be an independent prognostic marker for poor survival and may serve as a potential target for ESCC therapy.