Dataset Information

A Novel Androgen-Induced lncRNA FAM83H-AS1 Promotes Prostate Cancer Progression via the miR-15a/CCNE2 Axis.

ABSTRACT: Prostate cancer (PCa) is one of the most common types of tumors among males worldwide. However, the roles of long noncoding RNAs (lncRNAs) in PCa remain unclear. This study shows that lncRNA FAM83H-AS1 is upregulated in prostate adenocarcinoma, bladder urothelial carcinoma, and kidney renal papillary cell carcinoma samples. Androgen receptor (AR) signaling plays the most important role in PCa tumorigenesis and development. In this study, the results validate that AR signaling is involved in upregulating FAM83H-AS1 expression in PCa cells. Loss-of-function assays demonstrate that FAM83H-AS1 acts as an oncogene in PCa by modulating cell proliferation, cell cycle, and migration. Bioinformatics analysis demonstrates that FAM83H-AS1 is remarkably related to the regulation of the cell cycle and DNA replication through affecting multiple regulators related to these pathways, such as CCNE2. Mechanically, we found that FAM83H-AS1 plays its roles through sponging miR-15a to promote CCNE2 expression. These findings indicate that FAM83H-AS1 is a novel diagnostic and therapeutic marker for PCa.

SUBMITTER: Liu B

PROVIDER: S-EPMC7890020 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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A Novel Androgen-Induced lncRNA FAM83H-AS1 Promotes Prostate Cancer Progression <i>via</i> the miR-15a/CCNE2 Axis.

Liu Bo B Qian Duocheng D Zhou Weidong W Jiang Huiyang H Xiang Zhendong Z Wu Denglong D

Frontiers in oncology 20210204

Prostate cancer (PCa) is one of the most common types of tumors among males worldwide. However, the roles of long noncoding RNAs (lncRNAs) in PCa remain unclear. This study shows that lncRNA FAM83H-AS1 is upregulated in prostate adenocarcinoma, bladder urothelial carcinoma, and kidney renal papillary cell carcinoma samples. Androgen receptor (AR) signaling plays the most important role in PCa tumorigenesis and development. In this study, the results validate that AR signaling is involved in upre ...[more]

PMID: 33614501

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Project description:A growing number of dysregulated long non‑coding (lnc)RNAs have been verified to serve an essential role in human prostate cancer. However, the underlying mechanisms of lncRNA MNX1 Antisense RNA 1 (MNX1‑AS1) in prostate cancer has not been explored. Therefore, the present study aimed to explore the function of MNX1‑AS1 in prostate cancer tumorigenesis and investigate the in‑depth mechanism. The expression of MNX1‑AS1, microRNA (miR)‑2113 and murine double min 2 (MDM2) in prostate cancer tissues and corresponding normal tissues were assessed by reverse transcription‑quantitative PCR. The protein expression levels of MDM2 were detected by western blotting. LNCaP and PC‑3 cells were transfected with short hairpin (sh)‑MNX1‑AS1, miR‑2113 mimics, miR‑2113 inhibitor and pCDH‑MDM2 vector using Lipofectamine® 3000. Cell proliferation, migration and invasion abilities were assessed by CCK‑8 assay, colony formation and Transwell assay, respectively. Dual luciferase reporter assay was carried out to confirm the putative targets of MNX1‑AS1 and miR‑2113. Tumor formation experiment in nude mice was applied to evaluate the tumor growth effect of MNX1‑AS1 in vivo. The expression of MNX1‑AS1 was significantly upregulated in the prostate cancer tissues and cell lines. MNX1‑AS1 knockdown suppressed the abilities of cell viability and migration and invasion in vitro and inhibited tumor growth in vivo. Additionally, luciferase reporter assay revealed that MNX1‑AS1 could target miR‑2113 and negatively interacted with miR‑2113 in prostate cancer cells. miR‑2113 directly targeted to MDM2 and negatively modulated the expression of MDM2. Rescue assays suggested that the viability, migration and invasion of impaired cells triggered by transfection with sh‑MNX1‑AS1 alone could be recovered by co‑transfection with sh‑MNX1‑AS1 + miR‑2113 inhibitor or sh‑MNX1‑AS1 + pCDH‑ MDM2 vector. The present study demonstrated that MNX1‑AS1 promoted prostate cancer progression through regulating miR‑2113/ MDM2 axis.

Project description:Accumulating evidences revealed that long noncoding RNAs (lncRNAs) have been participated in cancer malignant progression, including glioblastoma multiforme (GBM). Despite much studies have found the precise biological role in the regulatory mechanisms of GBM, however the molecular mechanisms, particularly upstream mechanisms still need further elucidated. RT-QPCR, cell transfection, western blotting and bioinformatic analysis were executed to detect the expression of EGR1, HNF1A-AS1, miR-22-3p and ENO1 in GBM. Cell proliferation assay, colony formation assay, wound healing, migration and invasion assays were performed to detect the malignant characters of GBM cells. The molecular regulation mechanism was confirmed by luciferase reporter assay, ChIP and RIP. Finally, orthotopic mouse models were established to examine the effect of HNF1A-AS1 in vivo. In the current study, we analyzed clinical samples to show that the HNF1A-AS1 expression is upregulated and associated with poor patient survival in GBM. Functional studies revealed that HNF1A-AS1 knockdown markedly inhibits malignant phenotypes of GBM cells, whereas overexpression of HNF1A-AS1 exerts opposite effect. Mechanistically, the transcription factor EGR1 forced the HNF1A-AS1 expression by directly binding the promoter region of HNF1A-AS1. Furthermore, combined bioinformatics analysis with our mechanistic work, using luciferase reporter assays and RIP, we first demonstrated that HNF1A-AS1 functions as a competing endogenous RNA (ceRNA) with miR-22-3p to regulate ENO1 expression in GBM cells. HNF1A-AS1 directly binds to miR-22-3p and significantly inhibits miR-22-3p expression, while ENO1 expression was increased. miR-22-3p inhibitor offsets the HNF1A-AS1 silencing induced suppression in malignant behaviors of GBM cells. ENO1 was verified as a direct target of miR-22-3p and its expression levels was negatively with the prognosis in GBM patients. Taken together, our study illuminated the definite mechanism of HNF1A-AS1 in promoting GBM malignancy, and provided a novel therapeutic target for further clinical application.

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Project description:BackgroundOsteosarcoma (OS) is the most common primary malignant bone tumor in young people. Tumor-associated macrophages (TAMs) have been reported to play an important role in the development of osteosarcoma. However, the detailed molecular mechanisms remain largely unknown and need to be elucidated. Recently, exosomes have been reported as the crucial mediator between tumor cells and the tumor microenvironment. And a lot of lncRNAs have been reported to act as either oncogenes or tumor suppressors in osteosarcoma. In this research, we aim to explore the role of macrophages-derived exosomal lncRNA in osteosarcoma development and further elucidated the potential molecular mechanisms involved.MethodsTAMs were differentiated from human mononuclear cells THP-1, and a high-throughput microarray assay was used to analyze the dysregulated lncRNAs and miRNAs in osteosarcoma cells co-cultured with macrophages-derived exosomes. Western blot, qRT-PCR assays, and Dual-luciferase reporter assay were used to verify the interaction among LIFR-AS1, miR-29a, and NFIA. Cck-8, EdU, colony formation assay, wound-healing, and transwell assay were performed to explore the characterize the proliferation and metastasis ability of OS cells. And qPCR, Western blots, immunohistochemistry, and cell immunofluorescence were used to detect the expression of relative genes or proteins.ResultsIn this study, we found that THP-1-induced macrophage-derived exosomes could facilitate osteosarcoma cell progression both in vitro and in vivo. Then, the results of the high-throughput microarray assay showed that LIFR-AS1 was highly expressed and miR-29a was lowly expressed. Furthermore, LIFR-AS1 was identified as a miR-29a sponge, and NFIA was validated as a direct target of miR-29a. Functional assays demonstrated that knockdown of exosomal LIFR-AS1 could attenuate the promotion effects of macrophages-derived exosomes on osteosarcoma cell progression and miR-29a inhibition could reserve the effect of LIFR-AS1-knockdown exosomes. Correspondingly, NFIA-knockdown could partially reverse the tumor inhibition effect of miR-29a on osteosarcoma cells.ConclusionsTaken together, macrophages-derived exosomal lncRNA LIFR-AS1 can promote osteosarcoma cell proliferation, invasion, and restrain cell apoptosis via miR-29a/NFIA axis, which can act as a potential novel therapeutic target for osteosarcoma therapy.

Dataset Information

A Novel Androgen-Induced lncRNA FAM83H-AS1 Promotes Prostate Cancer Progression via the miR-15a/CCNE2 Axis.

Publications

A Novel Androgen-Induced lncRNA FAM83H-AS1 Promotes Prostate Cancer Progression <i>via</i> the miR-15a/CCNE2 Axis.

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