Non-coding RNA Zinc Finger Antisense Research Articles

LncRNA ZFAS1 Alleviated NLRP3 Inflammasome-Mediated Pyroptosis through Regulating miR-96-5p/Smad7 Signaling in Allergic Rhinitis

Introduction: The NLR family pyrin domain containing 3 (NLRP3)-mediated pyroptosis was positively correlated with the allergic rhinitis progression and was reported to be regulated by SMAD family member 7 (Smad7). Bioinformatics analysis revealed that Smad7 might be targeted by miR-96-5p, and miR-96-5p might be targeted by long noncoding RNA zinc finger antisense 1 (ZFAS1). However, the effects and regulatory mechanisms of the ZFAS1/miR-96-5p/Smad7 functional axis in allergic rhinitis have not been investigated. Methods: Human nasal mucosa epithelial cell line RPMI 2650 and C57BL/6 mice were obtained for in vitro and in vivo studies. Dual-luciferase reporter assay and RNA immunoprecipitation were implemented for detecting molecular interactions. Cell counting kit-8 and flow cytometry were used for measuring cell viability and pyroptosis. ELISA was obtained for monitoring cytokine secretion. RT-qPCR and Western blot were examined for determining RNA and protein expression. Results: In vitro studies revealed that ZFAS1 was downregulated in interleukin (IL)-13-treated RPMI 2650 cells, while overexpression of ZFAS1 enhanced cell viability and inhibited NLRP3-mediated pyroptosis and inflammatory response. ZFAS1 directly inhibited miR-96-5p to suppress NLRP3-mediated pyroptosis in IL-13-treated RPMI 2650 cells. MiR-96-5p bound to the 3′-untranslated region of Smad7 and knockdown of Smad7 significantly reversed the effects of miR-96-5p depletion. Moreover, in vivo experiments further confirmed the findings of in vitro studies and showed ZFAS1 overexpression or miR-96-5p inhibition alleviated allergic rhinitis in vivo. Conclusion: ZFAS1 downregulated the expression of miR-96-5p to upregulate Smad7 level, which subsequently inhibited NLRP3-mediated pyroptosis and inflammatory response to ameliorate allergic rhinitis.

RETRACTED ARTICLE: Inhibition of Long non-coding RNA zinc finger antisense 1 improves functional recovery and angiogenesis after focal cerebral ischemia via microRNA-144-5p/fibroblast growth factor 7 axis

Statement of Retraction Tong Li, Bai Ling Qing, Yan Deng, Xian Ting Que, Cheng Zhi Wang, Hua Wen Lu, Shao Hua Wang & Zi Jun Wang (2022) Inhibition of Long non-coding RNA zinc finger antisense 1 improves functional recovery and angiogenesis after focal cerebral ischemia via microRNA-144-5p/fibroblast growth factor 7 axis, Bioengineered, 13:1, 1702-1716, DOI: 10.1080/21655979.2021.2018093 Since publication, significant concerns have been raised about the integrity of the data and reported results in the article. When approached for an explanation, the authors did not provide their original data or any necessary supporting information. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. All authors listed in this publication have been informed. We have been informed in our decision-making by our editorial policies and the COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

The role of blood lnc-ZFAS1 in acute ischemic stroke: correlation with neurological impairment, inflammation, and survival profiles.

BackgroundLong non‐coding RNA zinc finger antisense 1 (lnc‐ZFAS1) has been reported to inhibit neuronal damage in acute ischemic stroke (AIS). However, the role of lnc‐ZFAS1 in AIS patients remains unclear. Therefore, we assessed the relationship of lnc‐ZFAS1 with neurological impairment, inflammation, and prognosis in AIS patients.MethodsTotally, 241 AIS patients and 120 controls were enrolled. lnc‐ZFAS1 in peripheral blood mononuclear cells was evaluated using reverse transcription‐quantitative polymerase chain reaction. Besides, a 3‐year follow‐up was conducted to assess recurrence‐free survival (RFS) and overall survival (OS) in AIS patients.Resultslnc‐ZFAS1 was reduced in AIS patients compared to that in controls (Z = −10.693, p < 0.001). In AIS patients, lnc‐ZFAS1 was negatively correlated with National Institutes of Health Stroke Scale score (r s = −0.335, p < 0.001), C‐reactive protein (r s = −0.284, p < 0.001), tumor necrosis factor‐alpha (r s = −0.293, p < 0.001), interleukin‐1β (r s = −0.149, p = 0.021), and interleukin‐6 (r s = −0.161, p = 0.012), but not underlying diseases (all p > 0.05). Besides, lnc‐ZFAS1 was divided into high and low levels based on the median expression in AIS patients. Indeed, high lnc‐ZFAS1 predicted better RFS (χ 2 = 6.222, p = 0.013); the 1‐year, 2‐year, and 3‐year RFS rates were 94.2%, 88.3%, and 85.5%, respectively, in patients with high lnc‐ZFAS1, then 87.5%, 79.2%, and 71.6%, respectively, in those with low lnc‐ZFAS1. However, lnc‐ZFAS1 was not correlated with OS (χ 2 = 1.404, p = 0.236); the 1‐year, 2‐year, and 3‐year OS rates were 98.3%, 95.8%, and 94.0%, respectively, in patients with high lnc‐ZFAS1, then 96.7%, 93.9%, and 89.6%, respectively, in those with low lnc‐ZFAS1.ConclusionLower lnc‐ZFAS1 expression is connected with increased neurological impairment and inflammation as well as worse RFS in AIS patients.

ZFAS1 knockdown inhibits fibroblast-like synoviocyte proliferation, migration, invasion and inflammation, and promotes apoptosis via miR-3926/FSTL1 in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by joint disorders. Long non-coding RNA zinc finger antisense 1 (ZFAS1) is aberrantly expressed in numerous human diseases, including RA. The present study aimed to investigate the functions and underlying mechanisms of ZFAS1 in RA. Reverse transcription-quantitative PCR was performed to determine the expression levels of ZFAS1, microRNA (miR)-3926 and follistatin-like protein 1 (FSTL1). MTT assay, flow cytometric analysis and Transwell assay were performed to examine the proliferation, apoptosis, migration and invasion of fibroblast-like synoviocytes (FLSs), respectively. Western blotting was employed to measure the protein expression levels of cleaved caspase-3, interleukin (IL)-6, IL-1β, tumor necrosis factor-α and FSTL1. Dual-luciferase reporter assay was performed to verify the interaction between miR-3926 and ZFAS1 or FSTL1. The results demonstrated that ZFAS1 and FSTL1 were upregulated, and miR-3926 was downregulated in RA synovial tissues and RA-FLSs. ZFAS1 knockdown suppressed cell proliferation, migration, invasion and inflammatory cytokine production, and induced apoptosis in RA-FLSs. ZFAS1 acted as a sponge for miR-3926, and ZFAS1 overexpression abolished the impact of miR-3926 on the development of RA-FLSs. FSTL1 was a direct target of miR-3926, and the effect of FSTL1 knockdown on the progression of RA-FLSs was rescued by miR-3926 inhibition. Furthermore, ZFAS1 regulated FSTL1 expression levels via sponging miR-3926 in RA-FLSs. In conclusion, ZFAS1 knockdown inhibited RA-FLS proliferation, migration, invasion and inflammatory cytokine production, and induced apoptosis in RA via the miR-3926/FSTL1 axis.

Silencing long non-coding RNA zinc finger antisense 1 restricts secondary cerebral edema and neuron injuries after traumatic brain injury

ObjectiveTo investigate the interaction of long non-coding RNA zinc finger antisense 1 (lncRNA ZFAS1) in secondary cerebral edema (CE) and neuron injuries after traumatic brain injury (TBI) in a mouse model. MethodsTBI mouse models was established by free-fall strike. Adeno-associated virus-short hairpin-ZFAS1 was administrated into mice via intracerebral injection to downregulate lncRNA ZFAS1. LncRNA ZFAS1 in mouse brain was examined. Neurological severity score (NSS), cerebral water content (CWC) and lesion volume were measured. The number of TUNEL-positive cells in brain tissue was accessed. Bax and cleaved caspase-3 in brain tissues were measured by western blot analysis, and pro-inflammatory factor levels were detected. ResultsLncRNA ZFAS1 expression was upregulated in mouse brain tissues 3 days after TBI modelling. After the knockdown of lncRNA ZFAS1, NSS, CWC and lesion volume were decreased, apoptotic gene levels were decreased and pro-inflammatory cytokine levels were reduced, suggesting that lncRNA ZFAS1 knockdown could alleviate TBI-induced brain injuries in mice. ConclusionThis study demonstrated that silencing lncRNA ZFAS1 inhibited TBI by quenching apoptosis, reducing inflammatory response and improving the recovery of neurological function in TBI mice. LncRNA ZFAS1 might function as a possible curative management in secondary CE and neuron injury in TBI mice.

ZFAS1 Promotes Colorectal Cancer Metastasis Through Modulating miR-34b/SOX4 Targeting.

Colorectal cancer (CRC) belongs to one of gastric cancers that half of cases will develop metastasis, causing higher mortality or chemotherapy resistance. In the present study, the long noncoding RNA zinc finger antisense 1 (ZFAS1) was proved to have high expression level in CRC samples and in advanced stages. Additionally, it also indicated that p53 status is associated with ZFAS1 expression. Silencing ZFAS1 reduced both migration and invasion ability of DLD-1 and HCT-116 cells, which is relevant to the EMT process. In addition, it was confirmed that miR-34b, a tumor suppressor miRNA directly targeted ZFAS1 3' untranslated region (3'UTR) and inhibited ZFAS1 expression. Furthermore, miR-34b partially reversed the effect of ZFAS1 on migration and invasion ability in DLD-1 cells. Meanwhile, p53 status changes by overexpression vectors or siRNA turbulent ZFAS1 expression. Besides, it was found that in most cases, the oncogene SOX4 was directly targeted by miR-34b and positive correlated to ZFAS1 expression. Silencing ZFAS1 induced SOX4 expression in DLD-1 cells. Our data demonstrated the functions and mechanisms of ZFAS1 in CRC metastasis, illustrating miR-34b directly targets ZFAS1 and inhibits metastasis ability of CRC cells. SOX4 is also the direct downstream target of miR-34b, and silencing ZFAS1 can inhibit SOX4 though modulating miR-34b.

Long noncoding RNA ZFAS1 suppresses chondrocytes apoptosis via miR-302d-3p/SMAD2 in osteoarthritis

Osteoarthritis (OA) seriously affects people's quality of life due to joint pain, stiffness, disability, and dyskinesia worldwide. Long noncoding RNA zinc finger antisense 1 (ZFAS1) is downregulated and tightly associated with proliferation, migration, apoptosis, and matrix synthesis of chondrocyte in OA. However, the molecular mechanisms of ZFAS1 in OA remain unknown. The expression correlation between ZFAS1, miR-302d-3p, and SMAD2 in OA tissues was analyzed by Pearson correlation analysis. ZFAS1 was a lower expression, and expedited proliferation and repressed apoptosis of chondrocytes. MiR-302d-3p was a direct target of ZFAS1. MiR-302d-3p hindered proliferation and facilitated apoptosis of chondrocytes. MiR-302d-3p partially reversed the effect of ZFAS1 on proliferation and apoptosis of chondrocytes. SMAD2 was positively regulated by the ZFAS1/miR-302d-3p. MiR-302d-3p-mediated proliferation and apoptosis were partly abrogated by targeting SMAD2. ZFAS1 promoted chondrocytes proliferation and repressed apoptosis possibly by regulating miR-302d-3p/SMAD2 axis, providing a potential target for OA treatment.

Long non-coding RNA zinc finger antisense 1 expression associates with increased disease risk, elevated disease severity and higher inflammatory cytokines levels in patients with lumbar disc degeneration.

This study aimed to investigate the correlation of long noncoding RNA zinc finger antisense 1 (lncRNA ZFAS1) expression with disease risk, disease severity and inflammatory cytokines levels in lumbar disc degeneration (LDD) patients.83 LDD patients underwent surgery and 28 traumatized, non-LDD patients underwent lumbar disc surgery (controls) were consecutively enrolled in this case-control study. Lumbar disc tissue was obtained during surgery and herniated nucleus pulposus (HNP) was isolated to detect lncRNA ZFAS1 expression and inflammatory cytokines mRNA levels by RT-qPCR, and determine protein levels of inflammatory cytokines by western blot.HNP lncRNA ZFAS1 expression in LDD patients was up-regulated compared with controls (P < .001), and receiver operating characteristic (ROC) curve showed lncRNA ZFAS1 expression disclosed a good predictive value for LDD risk with area under curve (AUC) 0.753 (95% CI 0.646–0.859). And after adjustment by age, gender and body mass index (BMI), lncRNA ZFAS1 (P = .017) remained to be an independent predictive factor for higher LDD risk. In addition, lncRNA ZFAS1 expression was positively associated with Modified Pfirrmann Grade (P = .015). As to inflammatory cytokines, lncRNA ZFAS1 expression was observed to be positively correlated with TNF-α (P = .002), IL-1β (P = .007) and IL-6 (P = .015) mRNAs expressions while reversely associated with IL-10 mRNA level (P = .014); and lncRNA ZFAS1 expression was also positively correlated with protein levels of TNF-α (P = .038) and IL-6 (P = .027) while reversely associated with IL-10 protein expression (P = .039).lncRNA ZFAS1 expression associates with increased risk, elevated disease severity and higher inflammatory cytokines levels in LDD patients.

Knockdown of ZFAS1 suppresses the progression of acute myeloid leukemia by regulating microRNA-150/Sp1 and microRNA-150/Myb pathways

Leukemia is the most frequent malignancy in children with acute myeloid leukemia (AML) as the second commonest type. Long non-coding RNA zinc finger antisense 1 (ZFAS1) has been widely reported as an oncogenic factor in multiple malignancies including AML. However, the roles and molecular mechanisms of ZFAS1 in the tumorigenesis of AML are poor defined till now. In the present study, RT-qPCR assay showed that ZFAS1 was highly expressed in bone marrow of acute leukemia patients and AML cell lines. Loss-of-function analyses revealed that ZFAS1 knockdown inhibited proliferation and promoted apoptosis in AML cells and curbed AML xenograft growth in vivo. Bioinformatics analysis and luciferase reporter assay unveiled that microRNA-150 (miR-150) could interact with ZFAS1, Myb 3′ UTR and Sp1 3′ UTR. Moreover, ZFAS1 acted as a molecular sponge of miR-150, giving rise to the downregulation of miR-150 level and upregulation of Myb and Sp1 levels. Moreover, miR-150 overexpression resulted in the reduction of AML cell proliferative ability and the increase of cell apoptotic rate. Additionally, the inhibition of miR-150 abrogated ZFAS1 loss-mediated anti-leukemia effects. In summary, our data demonstrated that ZFAS1 knockdown hampered AML progression by regulating miR-150/Myb and miR-150/Sp1 pathways, providing some potential biomarkers or targets for the diagnosis and treatment of leukemia.

Long non-coding RNA ZFAS1 correlates with clinical progression and prognosis in cancer patients.

Dysregulation of long non-coding RNA zinc finger antisense 1 (ZFAS1) has been reported in many types of cancers. We performed a synthetic analysis to clarify its prognostic significance as a cancer molecular-marker. Several databases (including PubMed, Web of Science, Embase together with Wanfang and China National Knowledge Internet database) were retrieved to identify ZFAS1-related articles. A total of eight articles were included in this meta-analysis. Hazard ratios (HR) and 95% confidence intervals (CI) were applied to assess the association between ZFAS1 expression level and overall survival (OS). Odds ratios (OR) were calculated with RevMan 5.3 software to determine the relationship between ZFAS1 expression and clinicopathologic features. The pooled results of the meta-analysis indicated that high ZFAS1 expression level was positively correlated with poor OS (HR = 1.87, 95% CI: 1.38-2.36, p< 0.001) in human solid cancers. The statistical significance was also observed in subgroup analysis stratified by the cancer type, analysis method, sample size and follow-up time. Furthermore, the elevated ZFAS1 expression was significantly related to positive lymph node metastasis (OR = 4.18, 95% CI: 2.70-6.48, p< 0.001). The present results suggest that ZFAS1 might be served as a novel promising biomarker for prognosis in Chinese patients with solid cancers.

Overexpression of long non-coding RNA zinc finger antisense 1 in acute myeloid leukemia cell lines influences cell growth and apoptosis.

The association between long non-coding RNA zinc finger antisense 1 (ZFAS1) and acute myeloid leukemia (AML) has not yet been investigated. The present study aimed to assess the potential role of ZFAS1 in AML cell proliferation and apoptosis. The expression of ZFAS1 mRNA in various AML cell lines (HL-60, KG-1, ML-1 and SKNO-1) was measured by reverse transcription-quantitative polymerase chain reaction. The results showed that ZFAS1 expression was increased in all four human AML cell lines compared with the control cell lines (T lymphocytic leukemia or Burkitt's lymphoma). Transfection with small interfering RNA into human AML cells established ZFAS1 knockdown. A cell-counting kit-8 (CCK-8) assay was used to investigate the effect of ZFAS1 on AML cell proliferation and the effect of ZFAS1 on the cell cycle and cell apoptosis was assessed using flow cytometry. Notably, the CCK-8 assay demonstrated that ZFAS1 knockdown inhibited cell proliferation in HL-60 and SKNO-1 cell lines and flow cytometry analysis indicated that ZFAS1 knockdown induced AML cell cycle G1 phase arrest and triggered cell apoptosis. Therefore, the present study indicated that ZFAS1 promoted the proliferation and inhibited the apoptosis of AML cells.

Long non-coding ribonucleic acid zinc finger antisense 1 promotes the progression of colonic cancer by modulating ZEB1 expression.

Long non-coding RNA zinc finger antisense 1 (ZFAS1) is frequently amplified in hepatocellular carcinoma and promotes metastasis by increasing zinc finger E-box binding homeobox 1 (ZEB1), which can potentiate the progression of epithelial-to-mesenchymal transition (EMT). However, the expression pattern and role of ZFAS1 in colonic cancer remains unknown. The present study aimed to investigate the role of ZFAS1 and its clinical significance in colonic cancer. Paired clinical colonic cancer tissue samples and clinicopathologic characteristics of 73 patients were analyzed. Quantitative real-time polymerase chain reaction analysis was used to evaluate expression levels of ZFAS1 in colonic cancer tissues, cell lines, and plasma. ZEB1 and EMT-related markers expression levels also were explored. Cell biology assays were used to explore the biologic consequences of ZFAS1 in regulating cell proliferation and invasion, as well as the roles in regulating EMT. Zinc finger antisense 1 was up-regulated in colonic cancer tissues compared with adjacent mucosa (P<0.01), and its expression level was significantly correlated with TNM stage, vascular invasion, and lymph node metastasis (P<0.05). ZFAS1 and ZEB1 were also increased in patients' plasma. Moreover, ZFAS1 promoted proliferation, invasion, and impeded apoptosis. Knockdown of ZFAS1 decreased expression of ZEB1 and increased the epithelial markers E-cadherin, ZO-1 while decreasing mesenchymal markers vimentin and N-cadherin. Long non-coding RNA ZFAS1 may function as an oncogene by modulating ZEB1 to induce EMT. Manipulation of ZFAS1 level may be a novel approach to suppress colonic cancer progression. In addition, ZFAS1 in plasma has the potential to be a diagnostic biomarker of colonic cancer.

Upregulation of long noncoding RNA zinc finger antisense 1 enhances epithelial-mesenchymal transition in vitro and predicts poor prognosis in glioma.

Increasing evidence indicates that long noncoding RNAs play important roles in development and progression of various cancers. Zinc finger antisense 1 is a novel long noncoding RNA whose clinical significance, biological function, and underlying mechanism are still undetermined in glioma. In this study, we reported that zinc finger antisense 1 expression was markedly upregulated in glioma and tightly correlated with clinical stage. Moreover, patients with high zinc finger antisense 1 expression had shorter survival. Multivariate Cox regression analysis provided a clue that, probably, zinc finger antisense 1 level could serve as an independent prognostic factor for glioma. Functionally, zinc finger antisense 1 acted as an oncogene in glioma because its knockdown could promote apoptosis and significantly inhibit cell proliferation, migration, and invasion. Furthermore, zinc finger antisense 1 silencing could result in cell cycle arrest at the G0/G1 phase and correspondingly decrease the percentage of S phase cells in both U87 and U251 cell lines. Moreover, it was found that silenced zinc finger antisense 1 could impair migration and invasion by inhibiting the epithelial-mesenchymal transition through reducing the expression of MMP2, MMP9, N-cadherin, Integrin β1, ZEB1, Twist, and Snail as well as increasing E-cadherin level in glioma. Taken together, our data identified that zinc finger antisense 1 might act as a valuable prognostic biomarker and potential therapeutic target for glioma.