Circulating long noncoding RNA, Zfpm2-As1, and XIST based on medical data analysis are potential plasma biomarkers for gastric cancer diagnosis.

BACKGROUND: Long noncoding RNAs (lncRNAs) participate in diseases, especially tumorigenesis, including gastric cancer (GC). Although lncRNAs in GC tissues have been extensively studied in previous research, the possible significance of circulating lncRNAs in diagnosing GC is still unknown. OBJECTIVE: The present work investigated lncRNAs ZFPM2-AS1 and XIST with high expression in GC tissues proved as potential plasma biomarkers from 20 early GC cases, 100 GC cases, and 90 normal subjects. METHODS: The possible correlation between ZFPM2-AS1 and XIST expression levels was analyzed with general characteristics and clinicopathological features. The performance in diagnosis was assessed according to receiver operating characteristic (ROC) analysis. RESULTS: According to the results, XIST and ZFPM2-AS1 expression remarkably increased within GC plasma relative to normal subjects (P< 0.01); besides, lncRNA XIST expression after surgery had a tendency of downregulation compared with preoperative levels (P< 0.05). Moreover, the area under ROC curve (AUC) values were 0.62 for ZFPM2-AS1 and 0.68 for XIST, while the pooled AUC value of CA-724 and two lncRNAs was 0.751. CONCLUSION: Circulating lncRNAs ZFPM2-AS1 and XIST can serve as the candidate plasma biomarkers used to diagnose GC.

ZFPM2-AS1: An Oncogenic Long Non-coding RNA in Multiple Cancer Types.

Long non-coding RNA (lncRNA) is a novel kind of RNA transcript with lengths greater than 200 nucleotides. Functionally, lncRNAs lack the potential to encode peptides or proteins. Previous studies unveiled that lncRNA participated in numerous physiological and pathological processes, including cancer, aging, and immune responses. Newly discovered long noncoding RNA zinc finger protein, Friend of GATA (FOG) family member 2-antisense 1 (ZFPM2-AS1), located on the 8q23 chromosome, acts as a tumor stimulator in various cancer types, including Breast Cancer (BC), Colorectal Cancer (CRC), Esophageal Squamous Cell Carcinoma (ESCC), Gastric Cancer (GC), glioma, hepatocellular carcinoma (HCC), Lung Adenocarcinoma (LUAD), melanoma, non-small cell lung cancer (NSCLC), Retinoblastoma (RB), Small Cell Lung Cancer (SCLC) and thyroid cancer. Accumulative evidence also elucidated that ZFPM2-AS1 dysregulation was related to tumor proliferative, migratory, invasive, anti-apoptotic, and pro-epithelial-tomesenchymal Transition (EMT) effects, larger tumor volume, higher tumor weight, advanced tumor stage, high rates of lymphatic metastasis, distant metastasis, poor prognosis, histological differentiation, higher TNM (tumor, node, metastases) stage, depth of tumor invasion, reduced overall and disease- free survival, vein invasion, and shorter 5-year overall survival. Mechanistically, ZFPM2-AS1 acted as a ceRNA to play its oncogenic role. Thus, this study summarized the specific mechanisms of the lncRNA ZFPM2-AS1 in the aforementioned cancer types to reveal its novel application in cancer diagnosis, treatment, and prognosis.

Genome stability­related lncRNA ZFPM2­AS1 promotes tumor progression via miR­3065­5p/XRCC4 in hepatocellular carcinoma.

Long noncoding RNAs (lncRNAs) have a certain link to genomic stability (GS). However, the regulatory relationship of lncRNAs and GS has not been thoroughly investigated in hepatocellular carcinoma (HCC). In the present study, samples were retrieved from The Cancer Genome Atlas with somatic mutations and lncRNA expression data. Cox regression analysis was used to identify independent prognostic factors. The RNA levels were determined by reverse transcription­quantitative PCR and protein levels were detected by western blot analysis. Cell Counting Kit­8 and colony­formation assays were used to assess cell viability. Cell migration was measured by wound­healing and Transwell assays. Cell apoptosis and cell­cycle progression were evaluated by flow cytometry. GS was detected by alkaline comet and chromosomal aberration assays. A xenograft model and lung metastasis model were used to assess the role of zinc finger protein, FOG family member 2 antisense 1 (ZFPM2­AS1) in tumor growth in vivo. The molecular mechanisms underlying the biological functions of ZFPM2­AS1 were investigated through bioinformatics prediction, RNA pull­down and luciferase reporter assays. A total of 85 genomic instability­related lncRNAs were identified and a prognostic model was developed. The prognostic model exhibited good predictive power (area under the receiver operating characteristic curve, 0.786). ZFPM2­AS1 was significantly upregulated in tumor tissues (P<0.001) and it promoted DNA damage repair (P<0.01) and tumor progression in vitro and in vivo. Luciferase reporter assays demonstrated that miR­3065­5p was able to bind directly with ZFPM2­AS1 and X­ray repair cross complementing 4 (XRCC4). ZFPM2­AS1 upregulated XRCC4 expression by acting as a sponge (P<0.001). In the present study, a prognostic model for HCC was developed and validated, and one lncRNA of its components was experimentally investigated. ZFPM2­AS1 regulates XRCC4 by sponging miR­3065­5p to promote GS and HCC progression.

Comprehensive analysis of ZFPM2-AS1 prognostic value, immune microenvironment, drug sensitivity, and co-expression network: from gastric adenocarcinoma to pan-cancers.

BACKGROUND: ZFPM2-AS1, as an oncogenic lncRNA, plays an essential role in the progression of several tumors. However, the prognostic significance, biological function, and molecular mechanism of ZFPM2-AS1 in most tumors have not been fully elucidated. METHODS: We analyzed differentially expressed immune-related lncRNAs (IRlncRNAs) and clustered gastric adenocarcinoma (GAC) samples based on these lncRNAs expression. Then, WGCNA and survival analysis were performed to determine key IRlncRNA (ZFPM2-AS1) in GAC. The comprehensive analysis was performed to evaluate the association between ZFPM2-AS1 expression and survival, tumor microenvironment (TME), immune-related factors, and related signal pathways in pan-cancers. Furthermore, we constructed a co-expression network of ZFPM2-AS1, and NUP107 and C8orf76 were identified as target mRNAs. We further evaluated the role of NUP107 and C8orf76 in the GAC microenvironment. More importantly, real-time polymerase chain reaction (qRT-PCR) was employed to validate ZFPM2-AS1, NUP107 and C8orf76 expression. RESULTS: ZFPM2-AS1 was remarkably overexpressed and correlated with poor overall survival in most tumors. Further analysis showed that ZFPM2-AS1 was related to various immune cells infiltrated in the microenvironment of most tumors. GSEA revealed that ZFPM2-AS1 in GAC was primarily involved in immune-related pathways. Furthermore, NUP107 and C8orf76 were identified as potential target mRNAs of ZFPM2-AS1, which was related to infiltrating immune cells in the GAC microenvironment. qRT-PCR verified that ZFPM2-AS, NUP107 and C8orf76 were highly expressed in gastric cancer cells. CONCLUSION: ZFPM2-AS1 could be a potential biomarker for cancer prognosis, and a promising immune target for cancer therapy. Furthermore, ZFPM2-AS1 might play an immunosuppressive role in the GAC microenvironment.

Long noncoding RNA ZFPM2-AS1 regulates renal cell carcinoma progression via miR-130a-3p/ESCO2.

Previous studies reported that long noncoding RNA (lncRNA) ZFPM2-AS1 is upregulated in renal cell carcinoma (RCC). However, the biological role of lncRNA ZFPM2-AS1 in RCC has not been explored. In this study, we investigated the role of lncRNA ZFPM2-AS1 in the progression of RCC. Quantitative real-time polymerase chain reaction was used for gene expression analysis, and functional assays including Cell Counting Kit-8 assay, flow cytometry-based apoptosis assay and transwell migration assays were performed to examine the malignant phenotypes. The functional interaction between ZFPM2-AS1 or miR-130A-3P and their targets was detected by dual-luciferase reporter assay. We found that the expressions of ZFPM2-AS1 and ESCO2 were upregulated in RCC tissues and cells, whereas miR-130a-3p was downregulated. The expression level of ZFPM2-AS1 is significantly associated with advanced TNM, distant metastasis, lymphatic metastasis, and a poor overall survival in RCC patients. Silencing ZFPM2-AS1 in RCC cells suppressed cell proliferation, invasion, and migration, and induced cell apoptosis. ZFPM2-AS1 interacted with miR-130A-3P and negatively regulated its expression in RCC cells. We further showed that ESCO2 was a downstream target of miR-130a-3p. Both miR-130a-3p inhibitor and ESCO2 overexpression could rescue the inhibitory effects of ZFPM2-AS1 knockdown in RCC cells. Together, our study demonstrates that ZFPM2-AS1 plays an oncogenic role in RCC progression via the miR-130a-3p/ESCO2 axis.

Long Non-coding RNA ZFPM2-AS1: A Novel Biomarker in the Pathogenesis of Human Cancers.

Due to their biological activities in regulating dosage compensation, epigenetics, and cell differentiation, long non-coding RNAs (lncRNA) have been recognized as important regulators of the beginning and development of human malignancies. LncRNA dysregulation has a significant impact on a range of cellular functions, including proliferation, migration, invasion, and anti-apoptosis activity. Recently, aberrant expression of the long non-coding RNA zinc finger protein multitype 2 antisense RNA 1 (ZFPM2-AS1) was observed in a range of solid tumors and correlated significantly with tumor size, histological differentiation, lymph node metastasis, malignant tumor (TNM) stage, short survival, and prognosis. Additional mechanical analysis indicated that ZFPM2-AS1 was involved in several cellular activities, including proliferation, migration, invasion, cell cycle progression, and apoptosis, through microRNAs (miRNAs), signaling pathways, and other biological components or proteins. This review summarizes the current status of research on ZFPM2-AS1 in various human malignancies and discusses its mechanism of action and clinical significance in tumor development and progression.

lncRNA ZFPM2-AS1 promotes retinoblastoma progression by targeting microRNA miR-511-3p/paired box protein 6 (PAX6) axis.

Long non-coding RNAs (lncRNAs) have been shown to play crucial roles in retinoblastoma progression. In this study, we aimed to investigate the mechanism of lncRNA ZFPM2-AS1 (ZFPM2-AS1) in retinoblastoma progression. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blotting assays were performed to determine the expression of lncRNA, microRNA (miRNA), mRNA, and protein. The changes in cell proliferation, apoptosis, and cell migration were assessed by functional experiments. The interaction between ZFPM2-AS1, miR-511-3p, and paired box protein 6 (PAX6) was confirmed by a luciferase assay. Our study found that ZFPM2-AS1 and PAX6 were upregulated, whereas miR-511-3p was downregulated in retinoblastoma. ZFPM2-AS1 inhibition decreased the viability and migration of retinoblastoma cells. We also found that ZFPM2-AS1 targets miR-511-3p to upregulate PAX6 in Y79 and SO-RB50 cells. Moreover, we demonstrated that inhibiting miR-511-3p reversed the negative effects of silencing ZFPM2-AS1 and PAX6 on retinoblastoma cell viability and migration. In conclusion, retinoblastoma development is regulated by the ZFPM2-AS1/511-3p/PAX6 axis.

SP1-induced lncRNA ZFPM2 antisense RNA 1 (ZFPM2-AS1) aggravates glioma progression via the miR-515-5p/Superoxide dismutase 2 (SOD2) axis.

Glioma is a common life-threatening tumor with high malignancy and high invasiveness. LncRNA ZFPM2 antisense RNA 1 (ZFPM2-AS1) was confirmed to be implicated in numerous tumors, while its biological function and mechanism have not been thoroughly understood in glioma. The gene expression was measured by RT-qPCR. Cell proliferation, cell cycle, and cell apoptosis of glioma cells were validated by CCK-8, colony formation, flow cytometry and TUNEL assays. The effect of ZFPM2-AS1 on tumor growth was verified by in vivo assay. The exploration on ZFPM2-AS1-mediated mechanism was carried out via ChIP, luciferase reporter, and RIP assays. In the present study, ZFPM2-AS1 was demonstrated as a highly-expressed lncRNA in glioma tissues and cells. ZFPM2-AS1 silencing suppressed cell proliferation and cell cycle, but facilitated cell apoptosis. In addition, the inhibitive effect of silenced ZFPM2-AS1 was also observed in tumor growth. Furthermore, we found that SP1 interacted with ZFPM2-AS1 promoter to transcriptionally activate ZFPM2-AS1 expression. Moreover, ZFPM2-AS1 was identified as a competing endogenous RNA (ceRNA) for miR-515-5p to target SOD2. Rescue assays verified that SOD2 overexpression partially abolished the suppressive impact of ZFPM2-AS1 silencing on glioma cell growth. In conclusion, this study corroborated the regulatory mechanism of SP1/ZFPM2-AS1/miR-515-5p/SOD2 axis in glioma, indicating that targeting ZFPM2-AS1 might be an effective way to treat glioma.

ZFPM2-AS1 transcriptionally mediated by STAT1 regulates thyroid cancer cell growth, migration and invasion via miR-515-5p/TUSC3.

Objective: Our purpose was to study the roles and molecular mechanisms of long non-coding RNA (lncRNA) ZFPM2 Antisense RNA 1 (ZFPM2-AS1) in thyroid cancer. Methods: Firstly, the expression of ZFPM2-AS1, miR-515-5p and TUSC3 was detected in thyroid cancer tissues and cells. Secondary, their biological functions (proliferation, apoptosis, migration and invasion) were analyzed by a serious of functional experiments including cell counting kit-8 (CCK-8), clone formation, 5-Ethynyl-2'-deoxyuridine (EdU), enzyme-linked immunosorbent assay (ELISA), wound healing and Transwell assays. Thirdly, the mechanisms of STAT1/ZFPM2-AS1 and ZFPM2-AS1/miR-515-5p/TUSC were validated using chromatin immunoprecipitation (CHIP), pull-down and luciferase reporter assays. Results: ZFPM2-AS1 and TUSC were both highly expressed and miR-515-5p was down-regulated in thyroid cancer tissues as well as cells. Their knockdown weakened thyroid cancer cell growth, migration, and invasion. ZFPM2-AS1 was mainly distributed in the nucleus and cytoplasm of thyroid cancer cells. Mechanistically, up-regulation of ZFPM2-AS1 was induced by transcription factor STAT1 in line with CHIP and luciferase reporter assays. Furthermore, as a sponge of miR-515-5p, ZFPM2-AS1 decreased the ability of miR-515-5p to inhibit TUSC3 expression by pull-down, luciferase reporter and gain-and-loss assays, thereby promoting malignant progression of thyroid cancer. Conclusion: ZFPM2-AS1 acted as an oncogene in thyroid cancer, which was transcriptionally mediated by STAT1. Furthermore, ZFPM2-AS1 weakened the inhibitory effect of miR-515-5p on TUSC3. Thus, ZFPM2-AS1 could be an underlying biomarker for thyroid cancer.

ZFPM2-AS1 facilitates cell proliferation and migration in cutaneous malignant melanoma through modulating miR-650/NOTCH1 signaling.

Aberrant expression of long non-coding RNA (lncRNA) zinc finger protein, FOG family member 2 antisense RNA 1 (ZFPM2-AS1) has been identified in many tumors, but its role in cutaneous malignant melanoma remains largely obscure. Our present study was intended to unveil the role and potential mechanism of ZFPM2-AS1 in cutaneous malignant melanoma. RT-qPCR was utilized to analyze ZFPM2-AS1 expression in cutaneous malignant melanoma cells. Cell counting kit-8 (CCK-8), colony formation, flow cytometry, and transwell analyses were utilized to assess ZFPM2-AS1 function on cell proliferation, apoptosis, and migration. Luciferase reporter, RNA immunoprecipitation, and RNA-pull down assays were applied to probe the regulatory mechanism of ZFPM2-AS1 in cutaneous malignant melanoma cells. Up-regulation of ZFPM2-AS1 was discovered in cutaneous malignant melanoma cells. ZFPM2-AS1 deletion restrained cell proliferation, migration, and elevated cell apoptosis in cutaneous malignant melanoma. ZFPM2-AS1 regulated notch receptor 1 (NOTCH1) to activate the NOTCH pathway. ZFPM2-AS1 acted as a competing endogenous RNA (ceRNA) to affect NOTCH1 expression via sponging miR-650. Collectively, ZFPM2-AS1 exerted an oncogenic role in cutaneous malignant melanoma progression via targeting miR-650/NOTCH1 signaling. Our study might offer a novel sight for cutaneous malignant melanoma treatment.

ZFPM2-AS1 promotes the proliferation, migration, and invasion of human non-small cell lung cancer cells involving the JAK-STAT and AKT pathways.

PURPOSE: Recent studies have determined that long non-coding RNAs (lncRNAs) are potential prognostic biomarkers for non-small cell lung cancers (NSCLCs). The purpose of this study was to analyze the function and associated pathways of zinc finger protein multitype 2 antisense RNA 1 (ZFPM2-AS1) in NSCLC cells. METHODS: We used qRT-PCR to analyze ZFPM2-AS1's transcription level. Its proliferation, migration, and invasion capacities were determined using MTT, colony forming, wound healing, and transwell assays. We additionally analyzed the correlation between ZFPM2 and immune infiltration using the Tumor Immune Estimation Resource (TIMER) database, and the protein expression levels using Western blots. RESULTS: We found that ZFPM2-AS1 expression in NSCLC specimens and cell lines was elevated compared to the control group. ZFPM2-AS1 is an oncogene and independent prognostic predictor of poor survival in NSCLCs, and its expression had a positive correlation with tumor size and lymph node metastasis in our clinical data. MTT, colony forming, wound healing, and transwell assays showed a positive correlation between ZFPM2-AS1 expression and the proliferation, migration, and invasion of NSCLC cells in the presence and absence of interferon- (IFN-γ). Using the TIMER database, we hypothesized that ZFPM2 was negatively correlated with ZFPM2-AS1 expression, as well as the immune infiltration levels in lung adenocarcinoma (LUAD). Finally, we found that ZFPM2-AS1 negatively regulated ZFPM2 expression, and had a positive correlation with PD-L1 expression through the JAK-STAT and AKT pathways. CONCLUSION: Our study confirmed that ZFPM2-AS1 promotes the proliferation, migration, and invasion of NSCLC cells via the JAK-STAT and AKT pathways. Further research on the ZFPM2-AS1 pathway regulation mechanism is needed.

Long noncoding RNA ZFPM2-AS1 acts as a miRNA sponge and promotes cell invasion through regulation of miR-139/GDF10 in hepatocellular carcinoma.

BACKGROUND: Emerging evidence has shown that dysregulated expression of long noncoding RNAs (lncRNAs) is implicated in liver hepatocellular carcinoma (HCC). However, the role and molecular mechanism of differentially expressed lncRNAs in HCC has not been fully explained. METHODS: The expression profiles of lncRNAs in HCC samples were derived from microarrays analysis or downloaded from The Cancer Genome Atlas (TCGA), and their correlation with prognosis and clinical characteristics were further analyzed. Silencing of lncRNA ZFPM2-AS1 was conducted to assess the effect of ZFPM2-AS1 in vitro. The miRcode and Target Scan databases were used to determine the lncRNA-miRNA-mRNA interactions. The biological functions were demonstrated by luciferase reporter assay, western blotting, PCR and rescue experiments. RESULTS: The expression level of lncRNA ZFPM2-AS1 was significantly higher in HCC tissues than in adjacent normal tissues, and higher ZFPM2-AS1 was remarkably related to poor survival. Functionally, silencing of lncRNA ZFPM2-AS1 inhibited cell proliferation, migration, invasion and promoted cell apoptosis in vitro. Bioinformatics analysis based on the miRcode and TargetScan databases showed that lncRNA ZFPM2-AS1 regulated GDF10 expression by competitively binding to miR-139. miR-139 and downregulated GDF10 reversed cell phenotypes caused by lncRNA ZFPM2-AS1 by rescue analysis. CONCLUSIONS: ZFPM2-AS1, an upregulated lncRNA in HCC, was associated with malignant tumor phenotypes and worse patient survival. ZFPM2-AS1 regulated the progression of HCC by acting as a competing endogenous RNA (ceRNA) to competitively bind to miR-139 and regulate GDF10 expression. Our study provides new insight into the posttranscriptional regulation mechanism of lncRNA ZFPM2-AS1 and suggests that ZFPM2-AS1/miR-139/GDF10 may act as a potential therapeutic target and prognostic biomarker for HCC.

Bioinformatics analyses and biological function of lncRNA ZFPM2-AS1 and ZFPM2 gene in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) remains one of the most lethal malignant tumors worldwide; however, the etiology of HCC still remains poorly understood. In the present study, cancer-omics databases, including The Cancer Genome Atlas, GTEx and Gene Expression Omnibus, were systematically analyzed in order to investigate the role of the long non-coding RNA (lncRNA) zinc finger protein, FOG family member 2-antisense 1 (ZFPM2-AS1) and the zinc finger protein, FOG family member 2 (ZFPM2) gene in the occurrence and progression of HCC. It was identified that the expression levels of lncRNA ZFPM2-AS1 were significantly increased in HCC tissues, whereas expression levels of the ZFPM2 gene were significantly decreased in HCC tissues compared with normal liver tissues. Higher expression levels of ZFPM2-AS1 were significantly associated with a less favorable prognosis of HCC, whereas higher expression levels of the ZFPM2 gene were associated with a more favorable prognosis of HCC. Genetic alterations in the ZFPM2 gene may contribute to a worse prognosis of HCC. Validation of the GSE14520 dataset also demon stared that ZFPM2 gene expression levels were significantly decreased in HCC tissues (P<0.001). The receiver operating characteristic (ROC) analysis of the ZFPM2 gene indicated high accuracy of this gene in distinguishing between HCC tissues and non-tumor tissues. The areas under the ROC curves were >0.8. Using integrated strategies, the present study demonstrated that lncRNA ZFPM2-AS1 and the ZFPM2 gene may contribute to the occurrence and prognosis of HCC. These findings may provide a novel understanding of the molecular mechanisms underlying the occurrence and prognosis of HCC.

YY1-induced lncRNA ZFPM2-AS1 facilitates cell proliferation and invasion in small cell lung cancer via upregulating of TRAF4.

BACKGROUND: Newly identified lncRNA zinc finger protein, FOG family member 2 antisense RNA 1 (ZFPM2-AS1) is identified as an oncogenic gene. However, the role of ZFPM2-AS1 in small cell lung cancer (SCLC) is poorly comprehended. METHODS: The expression of genes in SCLC tissues and cells was measured by qRT-PCR. Colony formation, EdU, CCK-8, transwell and wound healing as well as in vivo assays revealed the function of ZFPM2-AS1 in SCLC. ChIP, luciferase reporter, RIP and RNA pull down assays demonstrated the binding relation among genes. RESULTS: ZFPM2-AS1 was significantly upregulated in SCLC tissues and cells. ZFPM2-AS1 deficiency attenuated SCLC cell proliferation, invasion and migration. In addition, ZFPM2-AS1 was transcriptionally activated by Yin Yang 1 (YY1) factor. Further, miR-3612 was confirmed as downstream miRNA of ZFPM2-AS1. Moreover, TNF receptor associated factor 4 (TRAF4) was the target gene of miR-3612 in SCLC. ZFPM2-AS1, miR-3612 and TRAF4 jointly constituted a competing endogenous RNA (ceRNA) network in SCLC. Finally, TRAF4 could countervail ZFPM2-AS1 downregulation-mediated function on SCLC cell proliferation and invasion in vitro and tumor growth in vivo. CONCLUSION: Our study elucidated the oncogenic effect of ZFPM2-AS1 in SCLC progression, indicating it may be a therapeutic target for SCLC.

ZFPM2-AS1 facilitates cell growth in esophageal squamous cell carcinoma via up-regulating TRAF4.

Emerging evidence has confirmed that long noncoding RNAs (lncRNAs) are strongly involved in tumor initiation and development. LncRNA ZFPM2 antisense RNA 1 (ZFPM2-AS1) has been identified as a tumor facilitator in some cancers; nevertheless, its functional significance and regulatory mechanism remain greatly unclear in esophageal squamous cell carcinoma (ESCC). Here, we detected ZFPM2-AS1 expression in ESCC cell lines using qRT-PCR. ZFPM2-AS1 knockdown models were established for investigating the biological function of ZFPM2-AS1 in ESCC cells. The association between miR-3612 and ZFPM2-AS1 or TRAF4 was assessed by RNA pull-down and luciferase reporter assays. The present study indicated that ZFPM2-AS1 was significantly up-regulated in ESCC cells. Functional assays manifested that ZFPM2-AS1 knockdown restrained cell proliferation, migration and invasion, and facilitated cell apoptosis in ESCC. Mechanistically, ZFPM2-AS1 promoted ESCC cell growth and up-regulated TRAF4 to trigger NF-κB pathway by sequestering miR-3612. Besides, miR-3612 was confirmed to be a tumor inhibitor in ESCC. Through restoration experiments, we observed that TRAF4 overexpression could recover the suppressive effect of ZFPM2-AS1 on ESCC cell growth. Collectively, all the results suggested that ZFPM2-AS1 was an oncogene in ESCC cell growth by up-regulating TRAF4 and activating NF-κB pathway.

LncRNA ZFPM2-AS1 promotes lung adenocarcinoma progression by interacting with UPF1 to destabilize ZFPM2.

Lung adenocarcinoma (LUAD), a histological subclass of non-small-cell lung cancer, is globally the leading cause of cancer-related deaths. Long noncoding RNAs (lncRNAs) are emerging as cancer regulators. Zinc finger protein multitype 2 antisense RNA 1 (ZFPM2-AS1) is an oncogene in gastric cancer, but its functions have not been investigated in LUAD. We showed that ZFPM2-AS1 expression is high in LUAD samples based on GEPIA database (http://gepia.cancer-pku.cn/) and validated ZFPM2-AS1 upregulation in LUAD cell lines. Functionally, ZFPM2-AS1 facilitated proliferation, invasion, and epithelial-to-mesenchymal transition of LUAD cells. Thereafter, we found that ZFPM2 was negatively regulated by ZFPM2-AS1, and identified the suppressive effect of ZFPM2 regulation by ZFPM2-AS1 on LUAD progression. Mechanistically, we showed that ZFPM2-AS1 interacted with up-frameshift 1 (UPF1) to regulate mRNA decay of ZFPM2. Rescue assays in vitro and in vivo confirmed that ZFPM2-AS1 regulated LUAD progression and tumor growth through ZFPM2. Taken together, our findings demonstrate a role for the ZFPM2-AS1-UPF1-ZFPM2 axis in LUAD progression, suggesting ZFPM2-AS1 as a new potential target for LUAD treatment.

lncRNA ZFPM2-AS1 promotes proliferation via miR-18b-5p/VMA21 axis in lung adenocarcinoma.

Lung cancer has been proved to be one of the most common kinds of cancers around the globe. Meanwhile, as the predominant type of lung cancer, lung adenocarcinoma (LUAD) has received increasing attention in cancer research. Long noncoding RNAs (lncRNAs) are known to be associated with oncogenesis and progression of various cancers. However, many lncRNAs have not been thoroughly detected in LUAD. In this study, through bioinformatics analysis we found that zinc finger protein multitype 2 antisense RNA 1 (ZFPM2-AS1) was associated with poor prognosis of LUAD patients. Also, ZFPM2-AS1 was detected to be overexpressed in LUAD tissues and cells. Furthermore, ZFPM2-AS1 could promote the proliferation of LUAD cells. Next, miR-18b-5p was found to bind with and negatively regulated by ZFPM2-AS1. VMA21, target gene of miR-18b-5p, could bind with and be negatively regulated by miR-18b-5p. More importantly, both ZFPM2-AS1 and VMA21 were found to be attached to the RNA-induced silencing complex constructed from miR-18b-5p and Ago2. Also, ZFPM2-AS1 could regulate the expression of VMA21. Therefore, ZFPM2-AS1 were confirmed to regulate VMA21 by competitively binding with miR-18b-5p. Finally, rescue assays confirmed that ZFPM2-AS1 could regulate LUAD cell proliferation via miR-18b-5p/VMA21 axis.

Long noncoding RNA ZFPM2-AS1 is involved in lung adenocarcinoma via miR-511-3p/AFF4 pathway.

Lung cancer is the dominating cause of cancer-induced death and can be classified into small cell lung cancer and non-small cell lung cancer (NSCLC). Lung adenocarcinoma (LUAD) is the most common histological subtype of NSCLC and its pathology remains unclear. Mounting reports have revealed that lncRNAs could regulate cellular activities in cancers. Yet the role of ZFPM2 antisense RNA 1 (ZFPM2-AS1) in LUAD has not been elucidated. Using GEPIA online dataset, we identified the amplification of ZFPM2-AS1 in LUAD tissues. Through quantitative real-time reverse transcription-polymerase chain reaction analysis, we observed an upregulation of ZFPM2-AS1 in LUAD cell lines. Conducting loss-of-function assays, we found that ZFPM2-AS1 depletion impaired cell viability, suppressed cell migration, and reversed epithelial-mesenchymal transition progress in LUAD cells. Mechanism investigation manifested that ZFPM2-AS1 was distributed in the cytoplasm of LUAD cells. Moreover, ZFPM2-AS1 functioned as a molecular sponge of miR-511-3p, which was a suppressor in LUAD. Moreover, ZFPM2-AS1 sponged miR-511-3p and thereby deregulated AF4/FMR2 family member 4 (AFF4), a target of miR-511-3p. At length, rescue assays indicated that AFF4 overexpression revived the inhibiting effects of ZFPM2-AS1 knockdown on the biological processes in LUAD. All in all, this study uncovered the function and the mechanism of ZFPM2-AS1 in LUAD.