ZFAS1 functions as an oncogenic long non-coding RNA in bladder cancer

Bao

Cancer Biology & Therapy

et al. 2019

It is verified that long non-coding RNAs (lncRNAs) play crucial roles in various cancers. LncRNA LEF1-AS1 is a reported oncogene in colorectal cancer and glioblastoma. In this study, we unveiled that LEF1-AS1 markedly increased in oral squamous cell carcinoma (OSCC) tissues and cell lines. Besides, OSCC patients with high levels of LEF1-AS1 were apt to poor prognosis. Functionally, LEF1-AS1 knockdown inhibited cell survival, proliferation and migration, whereas enhanced cell apoptosis and induced G0/G1 cell cycle arrest in vitro. Consistently, LEF1-AS1 silence hindered tumor growth in vivo. Moreover, LEF1-AS1 inhibition stimulated the activation of Hippo signaling pathway through directly interacting with LATS1. Furtherly, we disclosed that LEF1-AS1 silence abolished the interaction of LEF1-AS1 with LATS1 while enhanced the binding of LATS1 to MOB, therefore promoting YAP phosphorylation but impairing YAP1 nuclear translocation. Additionally, we demonstrated that LEF1-AS1 regulated YAP1 translocation via a LATS1-dependent manner. Furthermore, we also uncovered that YAP1 overexpression abolished the suppressive impact of LEF1-AS1 repression on the biological processes of OSCC cells. In a word, we concluded that LEF1-AS1 served an oncogenic part in OSCC through suppressing Hippo signaling pathway by interacting with LATS1, suggesting the therapeutic and prognostic potential of LEF1-AS1 in OSCC.

Section: Introductionmentioning

confidence: 99%

Knockdown of lncRNA LEF1-AS1 inhibited the progression of oral squamous cell carcinoma (OSCC) via Hippo signaling pathway

Bao

Cancer Biology & Therapy

et al. 2019

“…The lncRNA ZFAS1, which is at located at 20q13, has been found stably expressed in many kinds of tumors [13]. Increasing evidence has shown that ZFAS1 is upregulated and involved in occurrence and development of several tumors, such as bladder cancer [14], cervical cancer [15], prostate cancer [16], and breast cancer [17]. Many studies have also shown that ZFAS1 serves as an oncogene in cancers, which could promote cell proliferation and invasion and inhibit cell apoptosis via regulating downstream protein expression [18].…”

Section: Introductionmentioning

confidence: 99%

Long Non-coding RNA Zinc Finger Antisense 1 (ZFAS1) Regulates Proliferation, Migration, Invasion, and Apoptosis by Targeting MiR-7-5p in Colorectal Cancer

Liu

et al. 2019

Med Sci Monit

Background Colorectal cancer (CRC) is one of the most common tumors, the causes of which remain unclear. Recently, many kinds of long non-coding RNAs (lncRNAs) have been identified to have an important role in the biological function of CRC. However, the effect of lncRNA zinc finger antisense 1 (ZFAS1) on development of CRC is still incompletely clear. Material/Methods Firstly, the expression of ZFAS1 and microRNA (miR)-7-5p in 40 CRC tissues and adjacent tissues was measured by real-time polymerase chain reaction. Then, we detected the cell proliferation, migration, invasion, and apoptosis in CRC cell lines by using Cell Counting Kit-8 assay, colony formation assay, flow analysis, and Transwell assay, respectively. Then, the relationship between ZFAS1 and miR-7-5p was verified by luciferase reporter assay. Finally, rescue experiments were conducted to confirmed that interaction of ZFAS1 and miR-7-5p in vitro . Results Our results showed that ZFAS1 was upregulated in CRC tissues, correlated with overall survival rates, and negatively related to the expression of miR-7-5p. It was verified that miR-7-5p was a direct target of ZFAS1 by bioinformatics analysis and luciferase reporter assay. In addition, knockdown of miR-7-5p inhibited proliferation, migration, and invasion, and promoted apoptosis in CRC cell lines, which could be rescue by miR-7-5p inhibitor. Conclusions Our study indicated that ZFAS1 directly targeted miR-7-5p, and knockdown of it could inhibit tumor growth, migration, invasion, and induce apoptosis in CRC. These data might provide a potent treatment mechanism or promising biomarker for CRC.

“…For instance, LncRNA-MALAT-1, which is highly expressed in bladder transitional cell carcinoma (BTCC), was found to play an important role in tumorigenesis and metastasis of BTCC, and the upregulation of MALAT1 were positively associated with advanced clinical and pathological stage and shorter survival of BTCC patients [7]. lncRNA-ZFAS1 (zinc finger antisense 1) was overexpressed in bladder cancer, and knockdown of ZFAS1 represses bladder cancer cell proliferation by upregulating the expression of KLF2 and NKD2, and inhibiting cell migration and invasion by downregulating ZEB1 and ZEB2 expression [8]. Thus, various lncRNAs were reported to be involved in carcinogenesis.…”

Section: Introductionmentioning

confidence: 99%

Higher Expression of Linc00152 Promotes Bladder Cancer Proliferation and Metastasis by Activating the Wnt/β-Catenin Signaling Pathway

et al. 2019

Background Recent studies have demonstrated that Linc00152 is highly expressed in multiple cancer types and its genes show tumor-promoting characteristics. However, the efficacy and biological mechanism of Linc00152 in bladder cancer remains unclear. Material/Methods We study investigated the relative expression and promoter methylation of Linc00152 in 126 cases of bladder cancer tissues by qRT-PCR and Bisulfite sequencing PCR. qRT-PCR was used to assess the relative expression of Linc00152 in 4 human bladder cancer cell lines. To explore the biological properties of Linc00152, we performed cell growth and soft-agar colony-formation assays, flow cytometry analyses, wound-healing assay, and Transwell assay. Western blot analysis was used to detect the underlying mechanisms of Linc00152 in bladder cancer. Results We found that Linc00152 was highly expressed in 126 cases of bladder carcinoma tissues (p<0.001) and 4 cell lines (p<0.01), and Linc00152 is more commonly expressed in patients with advanced-stage cancer (p=0.021). Knockdown of Linc00152 by using siRNAs in bladder cancer cell lines (T24 and HT-1197) suppressed cell viability and growth by causing cell cycle arrest and apoptosis (p<0.001), as well as inhibiting cell migration and invasion (p<0.001). In addition, the quantitative RT-PCR and Western blot results suggest that knockdown of Linc00152 reduced Wnt/β-Catenin signaling (p<0.001). Conclusions This research shows that Linc00152 is highly expressed in patients with bladder cancer and the possible carcinogenic effect of Linc00152 in bladder cancer occurs through activating the Wnt/β-Catenin signaling pathway, and could be a new biomarker for diagnosis and prevention of this cancer.