lncRNA Biomarkers of Glioblastoma Multiforme.

Long noncoding RNAs (lncRNAs) are RNA molecules of 200 nucleotides or more in length that are not translated into proteins. Their expression is tissue-specific, with the vast majority involved in the regulation of cellular processes and functions. Many human diseases, including cancer, have been shown to be associated with deregulated lncRNAs, rendering them potential therapeutic targets and biomarkers for differential diagnosis. The expression of lncRNAs in the nervous system varies in different cell types, implicated in mechanisms of neurons and glia, with effects on the development and functioning of the brain. Reports have also shown a link between changes in lncRNA molecules and the etiopathogenesis of brain neoplasia, including glioblastoma multiforme (GBM). GBM is an aggressive variant of brain cancer with an unfavourable prognosis and a median survival of 14-16 months. It is considered a brain-specific disease with the highly invasive malignant cells spreading throughout the neural tissue, impeding the complete resection, and leading to post-surgery recurrences, which are the prime cause of mortality. The early diagnosis of GBM could improve the treatment and extend survival, with the lncRNA profiling of biological fluids promising the detection of neoplastic changes at their initial stages and more effective therapeutic interventions. This review presents a systematic overview of GBM-associated deregulation of lncRNAs with a focus on lncRNA fingerprints in patients' blood.

LncRNA KTN1-AS1 facilitates esophageal squamous cell carcinoma progression via miR-885-5p/STRN3 axis.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies and frequent cause of cancer-related death worldwide. Long non-coding RNAs (lncRNAs) play regulatory roles and serve as biomarkers of multiple cancers, including ESCC. Our previous studies have confirmed that lncRNA Kinectin 1 antisense RNA 1 (KTN1-AS1) is highly expressed in ESCC and exerts oncogene function through RBBP4/HDAC1 complex. OBJECTIVE: Our present study focused on exploring a novel molecular mechanism of KTN1-AS1 in ESCC. METHODS: In this study, qRT-PCR assay, Western blot assay, Luciferase reporter assay, and RNA immunoprecipitation assay were conducted. RESULTS: We found that KTN1-AS1 could bind to miR-885-5p in ESCC cells, and miR-885-5p was low expressed in ESCC. Overexpression of miR-885-5p inhibited esophageal cancer cells proliferation and invasion in vitro. Mechanistic analysis demonstrated that miR-885-5p specifically targeted striatin 3 (STRN3), and KTN1-AS1/miR-885-5p promoted the EMT process by Hippo pathway in STRN3/YAP1 dependent manner. CONCLUSION: To sum up, KTN1-AS1 facilitates ESCC progression by acting as a ceRNA for miR-885-5p to regulate STRN3 expression and the Hippo pathway, and KTN1-AS1 maybe used as a promising therapeutic target for ESCC.

Evaluation of the expression level of some coding and non-coding genes in oral squamous cell carcinoma.

INTRODUCTION: Oral squamous cell carcinoma (OSCC) is the most common cancers arising from the head and neck region. There is growing evidence that lncRNAs play an important role in OSCC progression. The study aims to investigate correlations between the expression levels of LncRNAs of PARROT, MYCNUT, DANCR, and KTN1-AS1 with clinicopathological characteristics and finding suitable biomarkers for OSCC. MATERIAL AND METHOD: Total lncRNAs related to cancers and HNSC trascriptomics data were downloaded from lncRNADisease v2.0 database and xenabrowser, respectively. Then, ACO was perfomed on shared of LncRNAs between two databases. Finally, some lncRNAs were proposed as potential biomarkers. Thirty biopsies samples from patients with the OSCC and 30 healthy subjects were collected by the surgery. Questionnaires including clinical and demographic data were filled for all cases. Using Real-time PCR, the expression levels of PARROT, MYCNUT, DANCR, and KTN1-AS1 lncRNAs were quantified. RESULT: According to the results,17 novel gene symbol was identified.All the candidate lncRNAs the expression levels of PARROT, MYCNUT, DANCR, and KTN1-AS1 were remarkably upregulated in OSCC tumors in comparison with control group (RQ: 10.00 (P < 0.0001), RQ: 2.920 (P < 0.0001), RQ: 1.623 (P = 0.002), and 4.467 (P < 0.0001), respectively). Also, we found significant associations between tumor lncRNAs expression of PARRPT and DANCER and tumor metastasis (P = 0.009, and P = 0.005, respectively). Additionally, lncRNA KTN1-AS1 expression level was significantly higher in the patients with tumor size more than 3 cm, in comparison with tumor less than 3 cm (P = 0.005). According ROC analysis, all these candidate lncRNAs can be a significant predictor for OSCC (AUC of PARROT lncRNA = 69.72%, AUC of MYCNUT = 98.22%, AUC of DANCR = 74.83%, and AUC of KTN1-AS1 = 99.22%). CONCLUSION: we found that overexpression levels of PARROT, MYCNUT, DANCR, and KTN1-AS1 lncRNAs were correlated with poor clinicopathological characteristics in patients with OSCC. Also, PARROT, MYCNUT, DANCR, and KTN1-AS1 are novel biomarker for the detection of OSCC.

H3K27ac-activated lncRNA KTN1-AS1 aggravates tumor progression by miR-505-3p/ZNF326 axis in ovarian cancer.

Background: Numerous studies indicate that long noncoding RNA (lncRNA) is aberrantly expressed in ovarian cancer (OC). Our research investigated the regulatory role of lncRNA KTN1 antisense RNA1 (KTN1-AS1) in the progression of OC through the miR-505-3p/ZNF326 axis. Methods: Expression of KTN1-AS1, microRNA-505-3p (miR-505-3p), and zinc-finger protein-326 (ZNF326) in OC was evaluated by using RT-qPCR analysis. The biological function of KTN1-AS1 was inspected using the loss-of-function assay. Luciferase reporter assay and RIP assay were performed to determine the competitive endogenous RNA (ceRNA) network of KTN1-AS1/miR-505-3p/ZNF326. Results: The data showed that KTN1-AS1 and ZNF326 had a high expression in OC than in the normal tissue, and miR-505-3p exhibited a low expression in OC than in the normal tissue. The knockdown of KTN1-AS1 caused an inhibition in OC cell proliferation, migration, and invasion, and promoted cell apoptosis. In terms of mechanical exploration, KTN1-AS1 was transcriptionally activated by histone H3 on lysine 27 acetylation (H3K27ac) at the promoter region, and KTN1-AS1 increased ZNF326 expression by competitively adsorbing miR-505-3p. Conclusions: This study indicated that H3K27ac-induced lncRNA KTN1-AS1 expression, and facilitated proliferation, migration, and invasion of OC cells by the KTN1-AS1/miR-505-3p/ZNF326 axis.

Long non-coding RNA KTN1-AS1 promotes progression in pancreatic cancer through regulating microRNA-23b-3p/high-mobility group box 2 axis.

To explore the inhibitory effect of long non-coding RNA (LncRNA) antisense of KTN1 (KTN1-AS1) on the growth of pancreatic cancer (PC) cells by regulating the microRNA-23b-3p (miR-23b-3p)/high-mobility group box 2 (HMGB2) axis. The expression of KTN1-AS1 in tissues and cells was detected by qRT-PCR, and the relationship between KTN1-AS1 and clinicopathological data of patients with PC was analyzed. In addition, stable and transient overexpression and inhibition vectors were established and transfected into PC cells PANC-1, BxPC-3. CCK-8, transwell, and flow cytometry were responsible for the detection of proliferation, invasion, and apoptosis of transfected cells, respectively. The correlation of miR-23b-3p between KTN1-AS1 and HMGB2 was determined by dual luciferase reports, and the relationship between KTN1-AS1 and miR-23b-3p was further verified by RNA immunoprecipitation (RIP). The highly expressed KTN1-AS1 in PC patients was indicative of its high diagnostic value in this disease. Besides, it was found that KTN1-AS1 was linked with the pathological stage, differentiation degree and lymph node metastasis (LNM) of PC patients. Underexpressed KTN1-AS1 led to decreased proliferation and invasion ability of cells and increased apoptosis rate, while the effect of further overexpression of KTN1-AS1 on cells was the opposite. Dual luciferase reporter (DLR) assay confirmed that KTN1-AS1 could target miR-23b-3p, while miR-23b-3p could target HMGB2. Functional analysis showed that the overexpression of miR-23b-3p inhibited the expression of HMGB2 in PC cells and affected cell proliferation, invasion and apoptosis. Co-transfection of Sh-KTN1-AS1 and miR-23b-3p-mimics exhibited that up-regulation of KTN1-AS1 expression could reverse the effect of miR-23b-3p-mimics on PC cells.

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

BACKGROUND: Accumulating evidence support the hypothesis that long noncoding RNAs (lncRNAs) are involved in several physiological and pathological conditions, including cancer. Here, we investigated the potential role of lncRNAs in bladder cancer. METHODS: We first looked at available datasets retrieved from the TCGA database and discovered that the lncRNA KTN 1 antisense RNA 1 (KTN1-AS1) was significantly up-regulated in several cancer types including bladder cancer, but was decreased in some other tumors. Therefore, we focused our attention on KTN1-AS1. Using both in vitro and in vivo systems that allowed the modulation of KTN1-AS1 and expression of other relevant proteins, we investigated in-depth the role of KTN1-AS1 in bladder cancer (and the mechanism behind). We further investigated the potential KTN1-AS1-interacting proteins using RNA immunoprecipitation, and explored the KTN1-AS1-related epigenetic landscape (with a particular emphasis on acetylation) using chromatin immunoprecipitation (ChIP) assays. RESULTS: KTN1-AS1 silencing inhibited the proliferation, invasion, and migration of bladder cancer cells, while KTN1-AS1 overexpression had the obvious opposite effects. Mechanistically, KTN1-AS1 promoted the recruitment of EP300, a histone acetyltransferase that enriched acetylation of histone H3 at lysine 27 (H3K27Ac) in the KTN1 promoter region. This epigenetic modulation contributed to the up-regulation of KTN1, which affected bladder cancer growth and progression via the regulation of Rho GTPase (RAC1, RHOA, and CDC42)-mediated signaling. CONCLUSION: Overall, our data support the idea that the lncRNA KTN1-AS1 promotes bladder cancer tumorigenesis via modulation of the KTN1/Rho GTPase axis and is a promising new therapeutic target for the treatment of bladder cancer.

lncRNA KTN1­AS1 promotes glioma cell proliferation and invasion by negatively regulating miR­505­3p.

Glioblastoma (GBM) is one of the most prevalent and aggressive central nervous tumors with high mobility and mortality. The prognosis of patients with GBM is poor. It is therefore essential to explore the therapeutic strategies for the treatment of GBM. Previous studies have demonstrated that the long non­coding RNA (lncRNA) Kinectin 1­Antisense RNA 1 (KTN1­AS1) can participate in the development of several types of cancer. However, the underlying mechanism of KTN1­AS1 in GBM remains unknown. The present study aimed to determine the potential role of KTN1­AS1 in GBM. In this study, reverse transcription quantitative PCR analysis was conducted and the results demonstrated that KTN1­AS1 was upregulated in GBM tissues and cell lines compared with normal tissues and astrocytes (NHA). Furthermore, KTN1­AS1 knockdown decreased the viability and invasive ability of glioma cells in vitro and in vivo. In addition, high level of KTN1­AS1 was correlated with poor prognosis in TCGA GBM database. Furthermore, microRNA­505­3p (miR­505­3p) was a promising target of KTN1­AS1, and the suppressing effects of miR­505­3p on cell proliferation and invasive ability was reversed by downregulating KTN1­AS1. Taken together, the results from the present provided novel insights into the roles of KTN1­AS1 in GBM, and suggested that the KTN1­AS1/miR­505­3p axis may be considered as a novel therapeutic target for the treatment of patients with GBM.

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

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, loss-of-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.

Long noncoding RNA KTN1-AS1 promotes head and neck squamous cell carcinoma cell epithelial-mesenchymal transition by targeting miR-153-3p.

Aim: To explore the biological functions and clinicopathologic significance of the long noncoding RNA KTN1-AS1 in head and neck squamous cell carcinoma (HNSCC). Materials & methods: We assessed the effects of KTN1-AS1 and identified the target miRNA by bioinformatics analysis, luciferase reporter, RNA pull-down and RNA immunoprecipitation assays. The clinicopathologic features of KTN1-AS1 and its target miRNA were analyzed in HNSCC. Results:KTN1-AS1, a competing endogenous RNA, promoted cell proliferation, migration, invasion and epithelial-mesenchymal transition by sponging miR-153-3p in HNSCC. Dysregulation of SNAI1 and ZEB2 mediated the effect of KTN1-AS1 due to miR-153-3p exhaustion. The KTN1-AS1 and miR-153-3p combination can accurately diagnose HNSCC. Conclusion: The KTN1-AS1 and miR-153-3p combination could be a valuable diagnostic and prognostic predictor for HNSCC.

LncRNA KTN1-AS1 promotes tumor growth of hepatocellular carcinoma by targeting miR-23c/ERBB2IP axis.

Long non-coding RNAs (lncRNAs) are critical regulators in the tumorigenesis and metastasis of hepatocellular carcinoma (HCC). LncRNA KTN1 antisense RNA 1 (KTN1-AS1) has been reported to play an important role in colorectal cancer and correlates with unfavorable clinical outcomes of head and neck squamous cell carcinoma. However, the clinical significance and functional role of KTN1-AS1 in HCC are still unclear. Here, we found that KTN1-AS1 was a highly expressed lncRNA in HCC according to public available databases and our HCC cohort. Further analyses revealed that higher expression of KTN1-AS1 was observed in HCC tissues with large tumor size, high tumor grade and advanced TNM stage. Analysis of survival data indicated that high KTN1-AS1 expression was prominently correlated with poor clinical outcomes of HCC patients. Functionally, KTN1-AS1 knockdown suppressed cell proliferation and colony formation, and increased apoptosis of SMMC-7721 cells in vitro. Furthermore, silencing of KTN1-AS1 restrained tumor growth of HCC in vivo. Conversely, forced expression of KTN1-AS1 facilitated Huh7 cell proliferation and inhibited apoptosis. Mechanistically, KTN1-AS1 inversely regulated miR-23c abundance in HCC cells. Further evidence supported that KTN1-AS1 acted as a competing endogenous RNA (ceRNA) by directly sponging miR-23c in HCC cells. Interestingly, erbb2 interacting protein (ERBB2IP), a known target of miR-23c, was positively regulated by KTN1-AS1 and its restoration reversed KTN1-AS1 knockdown attenuated HCC cell growth. To conclude, our study sheds light on the novel function and underlying mechanism of KTN1-AS1 in HCC, which may accelerate the development of cancer therapy.