Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Han S

PROVIDER: S-EPMC7191191 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Han Shuhua S Cao Dandan D Sha Jun J Zhu Xiaoli X Chen Dongqin D

Molecular oncology 20200220 5

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 upregulati ...[more]

PMID: 31919993

Similar Datasets

Project description: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 transcription‑quantitative PCR and protein levels were detected by western blot analysis. Cell Counting Kit‑8 and colony‑formation assays were used to assess cell viability. Cell migration was measured by wound‑healing and Transwell assays. Cell apoptosis and cell‑cycle 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 (ZFPM2‑AS1) in tumor growth in vivo. The molecular mechanisms underlying the biological functions of ZFPM2‑AS1 were investigated through bioinformatics prediction, RNA pull‑down and luciferase reporter assays. A total of 85 genomic instability‑related 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). ZFPM2‑AS1 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 miR‑3065‑5p was able to bind directly with ZFPM2‑AS1 and X‑ray repair cross complementing 4 (XRCC4). ZFPM2‑AS1 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. ZFPM2‑AS1 regulates XRCC4 by sponging miR‑3065‑5p to promote GS and HCC progression.

Project description:ObjectivesLung adenocarcinoma (LUAD) exhibits a higher fatality rate among all cancer types worldwide, yet the precise mechanisms underlying its initiation and progression remain unknown. Mounting evidence suggests that long non-coding RNAs (lncRNAs) exert significant regulatory roles in cancer development and progression. Nevertheless, the precise involvement of lncRNA CYP4A22-AS1 in LUAD remains incompletely comprehended.MethodsBioinformatics analyses evaluated the expression level of CYP4A22-AS1 in lung adenocarcinoma and paracancer. The LUAD cell line with a high expression of CYP4A22-AS1 was constructed to evaluate the role of CYP4A22-AS1 in the proliferation and metastasis of LUAD by CCK8, scratch healing, transwell assays, and animal experiments. We applied transcriptome and microRNA sequencing to examine the mechanism of CYP4A22-AS1 enhancing the proliferation and metastasis of LUAD. Luciferase reporter gene analyses, west-blotting, and qRT-PCR were carried out to reveal the interaction between CYP4A22-AS1, miR-205-5p/EREG, and miR-34c-5p/BCL-2 axes.ResultsCYP4A22-AS1 expression was significantly higher in LUAD tissues than in the adjacent tissues. Furthermore, we constructed a LUAD cell line with a high expression of CYP4A22-AS1 and noted that the high expression of CYP4A22-AS1 significantly enhanced the proliferation and metastasis of LUAD. We applied transcriptome and microRNA sequencing to examine the mechanism of CYP4A22-AS1 enhancing the proliferation and metastasis of LUAD. CYP4A22-AS1 increased the expression of EREG and BCL-2 by reducing the expression of miR-205-5p and miR-34-5p and activating the downstream signaling pathway of EGFR and the anti-apoptotic signaling pathway of BCL-2, thereby triggering the proliferation and metastasis of LUAD. The transfection of miR-205-5p and miR-34-5p mimics inhibited the role of CYP4A22-AS1 in enhancing tumor progression.ConclusionThis study elucidates the molecular mechanism whereby CYP4A22-AS1 overexpression promotes LUAD progression through the miR-205-5p/EREG and miR-34c-5p/BCL-2 axes.

Project description:IntroductionColon adenocarcinoma (COAD) is the third most common tumor of the digestive tract. Recent studies reported that lncRNA's abnormal expression might play a vital role in the occurrence and development of COAD.MethodsIn the present study, we investigated the expression of ILF3-AS1 in COAD cell lines, human normal colon epithelial cell line, patient tumor tissues and adjacent normal tissues by real-time quantitative PCR (RT-qPCR). Small interfering RNAs (siRNAs) were transfected into COAD cells to inhibit the expression of ILF3-AS1. The effects of ILF3-AS1 on cell proliferation, migration, invasion and apoptosis were measured by CCK-8 assay, transwell migration and invasion assay, and flow cytometry apoptosis assay, respectively. The direct binding of ILF3-AS1 and miR-619-5p/CAMK1D was validated by the luciferase reporter assay. The expression of CAMK1D and epithelial-mesenchymal transformation (EMT)-related proteins was detected by Western Blot analysis. Besides, in vivo experiments were conducted to demonstrate the oncogenic role of ILF3-AS1 in COAD.ResultsThe results showed that the expression of ILF3-AS1 was significantly higher in COAD tissue than in normal adjacent samples, and this conclusion was confirmed in the available public datasets. After ILF3-AS1 knockdown, the proliferation of COAD cell lines SW480 and HT29 was significantly inhibited. At the same time, the apoptosis was increased, and the invasion and migration abilities were decreased. After further exploring the mechanisms, we found that ILF3-AS1 serves as a competitive endogenous RNA of mir-619-5p. It can bind to mir-619-5p and reduce its expression, thus regulating the target gene CAMK1D. In addition, we found that high expression of ILF3-AS1 was significantly associated with tumor grade, tumor size, and distant metastasis in COAD samples. In vivo experiments confirmed that ILF3-AS1 promotes tumor growth in COAD models.ConclusionThe present study demonstrated that ILF3-AS1 plays an oncogenic role in COAD through regulating the miR-619-5p/CAMK1D axis, and inhibition of ILF3-AS1 may pave the way for COAD treatment.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets