STAT1-induced upregulation of lncRNA KTN1-AS1 predicts poor prognosis and facilitates non-small cell lung cancer progression via miR-23b/DEPDC1 axis

Abstract

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.

The long noncoding RNA KTN1-AS1 promotes bladder cancer tumorigenesis via KTN1 cis-activation and the consequent initiation of Rho GTPase-mediated signaling

“…This lncRNA is first reported as differentially expressed in colorectal cancer cells and tissues (8). KTN1-AS1 is then reported to be upregulated in head and neck squamous cell carcinoma, hepatocellular carcinoma, and non-small cell lung cancer, and positively associated with tumorigenesis and unfavorable clinical outcomes (9)(10)(11)(12). Of note, most of these studies have reported that KTN1-AS1 acts as a competing endogenous RNA (ceRNA), competitively combining with miRNA response elements (MREs) to regulate downstream protein-coding gene expression.…”

“…These interactions between KTN1-AS1, miRNAs, and mRNAs generate complex regulatory axes and are involved in the regulation of cancer cell behavior (10)(11)(12).…”

“…Indeed, in this study gain/loss-of-function contexts proved that KTN1-AS1 promotes the proliferation and invasion of bladder cancer both in vitro and in vivo.The molecular mechanism behind this phenotype remained unknown thus far.LncRNAs have been proposed to have several diverse functions such as the organization of nuclear domains, the transcriptional regulation of genes in cis or in trans, and the regulation of proteins or RNA molecules(20). KTN1-AS1 has been reported to act as a competing endogenous RNA to regulate tumorigenesis and metastasis(10)(11)(12). However, none of these studies have uncovered whether (and how) KTN1-AS1 carries out other molecular functions, such as the transcriptional regulation of its neighboring gene KTN1.…”

Identification of a three-miRNA signature as a novel prognostic model for papillary renal cell carcinoma

“…Because of the significantly individual variation, a class of genetic markers including coding and non-coding genes attracted increasing attentions in the past few years [ 24 – 26 ]. Liu et al indicated lncRNA KTN1-AS1 played the remarkable roles on predicting the poor prognosis of non-small cell lung cancer and facilitate tumor progression through regulating miR-23b/DEPDC1 axis [ 27 ]. Zhou et al developed a profile of TILBlncSig consisting of eight long non-coding RNAs (lncRNAs) identified from 141 B cell specific lncRNAs and demonstrated the potential implications in prognosis of bladder cancer [ 28 ].…”

lncRNA KTN1‑AS1 promotes glioma cell proliferation and invasion by negatively regulating miR‑505‑3p

“…The lncRNA Kinectin 1-Antisense RNA 1 (KTN1-AS1) is located on chromosome 14 and was demonstrated to be upregulated in non-small cell lung cancer, hepatocellular carcinoma and head and neck squamous cell carcinoma, where it was confirmed to act as an independent prognostic factor ( 21 – 24 ). Previous studies reported that KTN1-AS1 promotes the development of hepatocellular carcinoma and non-small cell lung cancer ( 21 , 22 ). Jiang et al ( 23 ) also demonstrated that KTN1-AS1 can suppress the epithelial-mesenchymal transition in head and neck squamous cell carcinoma.…”