Long noncoding RNA ZFAS1 promotes tumorigenesis and metastasis in nasopharyngeal carcinoma by sponging miR-892b to up-regulate LPAR1 expression.

In this study, we explored the NPC-specific expression of ZFAS1 and the mechanism of ZFAS1-mediated growth, aggressiveness and tumorigenesis in NPC. The expression profile of lncRNAs was detected in NPC tissues and matching para-carcinoma tissues using microarray analysis. LncRNA-miRNA and miRNA-mRNA interaction networks were constructed using the miRcode v11 and TargetScanHuman v7.2 web server and then validated using dual-luciferase assay. Western blot and RT-qPCR were performed to detect protein and RNA expression. The effects of ZFAS1, miR-892b and LPAR1 dysregulation on the proliferative, migratory and invasive abilities of NPC cells were observed using colony formation, cell counting kit-8 (CCK-8) and transwell assays in vitro. In vivo, a xenograft nude mouse model was established to detect the impact of ZFAS1 dysregulation on the tumorigenicity of NPC cells. The expression of multiple lncRNAs, of which ZFAS1 was up-regulated, was dysregulated in NPC tissues. ZFAS1 directly targeted miR-892b, and miR-892b negatively regulated the expression of downstream LPAR1. The proliferation, migration and invasion of NPC cells could be largely enhanced by the downregulation of miR-892b as well as the up-regulation of ZFAS1 and LPAR1, while the overexpression of miR-892b and the downregulation of ZFAS1 and LPAR1 decreased these abilities. In nude mice, the growth of tumour xenografts formed by HONE1 cells was significantly suppressed when ZFAS1 was silenced. The study demonstrated that lncRNA ZFAS1 may act as a promoter of tumorigenesis and metastasis in nasopharyngeal carcinoma, by up-regulating the expression of LPAR1 in a miR-892b-dependent manner.

Peng J ，Liu F ，Zheng H ，Wu Q ，Liu S ... -  《-》

LncRNA XIST knockdown suppresses the malignancy of human nasopharyngeal carcinoma through XIST/miRNA-148a-3p/ADAM17 pathway in vitro and in vivo.

Long non-coding RNA (lncRNA) X inactivate-specific transcript (XIST) has been verified as an oncogenic gene in human cancers, including nasopharyngeal carcinoma (NPC). However, the role of XIST in NPC remains to be largely uncovered, as well as its underlying mechanism. Expression of XIST, miR-148a-3p and ADAM17 was detected using qPCR and western blot assay. Cell proliferation and apoptosis assay were measured with MTT and flow cytometry, separately. Migration and invasion abilities were examined by transwell assays. Epithelial-mesenchymal transition (EMT) was assessed by western blot analyzing levels of E-cadherin, N-cadherin and vimentin. The potential binding between miR-148a-3p and XIST/ADAM17 was validated by luciferase reporter assay, Ago2-RNA immunoprecipitation and RNA pull-down assay. Xenograft experiments were conducted to measure tumor growth. XIST was upregulated and miR-148a-3p was downregulated in NPC tissues and cell lines. Both XIST knockdown and miR-148a-3p overexpression promoted apoptosis, suppressed cell proliferation, migration, invasion, and EMT of NPC cells in vitro. In addition, miR-148a-3p was validated as a target of XIST, and silencing of miR-148a-3p could reverse XIST knockdown-mediated functions in SUNE-1 and CNE2 cells. Furthermore, miR-148a-3p was identified to target ADAM17, and ectopic expression of ADAM17 could abate miR-148a-3p-induced effects as well. Notably, ADAM17 was downregulated by XIST knockdown through upregulating miR-148a-3p. In vivo, XIST knockdown resulted in a slower tumor growth. Knockdown of XIST suppresses the malignant progression of NPC cells through targeting miR-148a-3p/ADAM17 axis both in vitro and in vivo.

Shi J ，Tan S ，Song L ，Song L ，Wang Y ... -  《-》

Long noncoding RNA cytoskeleton regulator RNA promotes cell invasion and metastasis by titrating miR-613 to regulate ANXA2 in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is one of the most frequent head and neck malignant tumors. Long noncoding RNAs play critical roles in tumorigenesis. Real-time quantitative PCR arrays were used to evaluate the expression levels of cytoskeleton regulator RNA (CYTOR) in NPC tissues and cells. Cell counting kit-8 and colony formation analyses were used to test the NPC cell viability, while wound healing and transwell assays were employed to detect cell invasion and migration ability. Luciferase reporter assay and Western blot analyses were employed to explore the relationships among CYTOR, miR-613, and ANXA2. We found that CYTOR expression was elevated both in NPC tissues and cells. Functional assays revealed that CYTOR promoted the invasion and migration of NPC cells. The established spontaneous lymph node metastasis model also confirmed that CYTOR promoted NPC cell metastasis in vivo. Mechanically, we found that the subcellular localization of CYTOR mostly occurred in the cell cytoplasm. Luciferase reporter and RIP assays confirmed that CYTOR functioned as the molecular sponge of miR-613. Subsequent experiments confirmed that ANXA2 was directly targeted by miR-613. Gain- and loss-of-function studies further confirmed that CYTOR induced the upregulation of ANXA2 by competitively binding to miR-613, thus leading to NPC metastasis. Our results highlight the importance of CYTOR in NPC development and provide new insights into potential therapeutic targets for NPC.

Chen W ，Du M ，Hu X ，Ma H ，Zhang E ，Wang T ，Yin L ，He X ，Hu Z ... -  《Cancer Medicine》

The long noncoding RNA ZFAS1 facilitates bladder cancer tumorigenesis by sponging miR-329.

The incidence and mortality rate of bladder cancer have dramatically expanded, so it's urgent to discover new biomarker and therapeutic target for bladder cancer. Recently, lncRNA has been identified as oncogene or tumor suppressor to regulate the tumorigenesis. LncRNA ZFAS1 has been confirmed as oncogene in various tumors. However, the expression, function, and underlying mechanism of ZFAS1 in bladder carcinogenesis have yet to be totally clarified. In the current study, our data demonstrated that ZFAS1 expression was significantly upregulated in bladder cancer tissues and cell lines. Furthermore, Kaplan-Meier analysis revealed that high ZFAS1 expression was significantly associated with unfavorable progression free survival (PFS) (P = 0.0034 < 0.01) and overall survival (OS) (P = 0.0041 < 0.01) of bladder cancer patients. Moreover, silencing of ZFAS1 expression could markedly suppress bladder cancer cells proliferation and colony formation, arrest cell cycle, promote cell apoptosis and inhibit cell migration in vitro. In addition, bioinformatics analysis, luciferase reporter assay, and pull down assay revealed that ZFAS1 straightly interacted with miR-329. Lastly, rescue experiments confirmed that miR-329 inhibitor reversed the tumor suppressing roles of ZFAS1 knockdown on bladder cancer cells. Collectively, our results illuminated that ZFAS1 could serve as an oncogene in the tumorigenesis of bladder cancer, and discovered the functional regulatory network of ZFAS1 sponging miR-329.

Wang JS ，Liu QH ，Cheng XH ，Zhang WY ，Jin YC ... -  《-》

Knockdown of lncRNA ZFAS1 inhibits progression of nasopharyngeal carcinoma by sponging miR-135a.

Wang M ，Ji YQ ，Song ZB ，Ma XX ，Zou YY ，Li XS ... -  《NEOPLASMA》