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

He, Hui; Wang, Yawei; Ye, Peng; Yi, Dehui; Cheng, Ying; Tang, Huiqin; Zhu, Zhi; Wang, Xun; Shi, Jin

doi:10.1186/s13046-020-01664-1

Cited by 68 publications

(60 citation statements)

References 33 publications

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“…For example, Zhe Li et al reported that LINC00624 enhances liver cancer progression by disrupting the histone deacetylase 6 (HDAC6)- tripartite motif containing 28 (TRIM28) - zinc finger potein 354C (ZNF354C) corepressor complex [ 6 ]. Hui He et al confirmed that lncRNA ZFPM2-AS1 acts as a miRNA sponge and promotes cell invasion through regulation of miR-139/growth differentiation factor 10 (GDF10) in HCC [ 7 ]. Our research team also discovered and studied the role of several lncRNAs in the progression of HCC in previous studies.…”

Section: Introductionmentioning

confidence: 99%

Long non-coding RNA MAPKAPK5-AS1/PLAGL2/HIF-1α signaling loop promotes hepatocellular carcinoma progression

Wang

Sun

Liu

et al. 2021

J Exp Clin Cancer Res

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Background Long non-coding RNAs (lncRNAs) are widely involved in human cancers’ progression by regulating tumor cells’ various malignant behaviors. MAPKAPK5-AS1 has been recognized as an oncogene in colorectal cancer. However, the biological role of MAPKAPK5-AS1 in hepatocellular carcinoma (HCC) has not been explored. Methods Quantitative real-time PCR was performed to detect the level of MAPKAPK5-AS1 in HCC tissues and cell lines. The effects of MAPKAPK5-AS1 on tumor growth and metastasis were assessed via in vitro experiments, including MTT, colony formation, EdU, flow cytometry, transwell assays, and nude mice models. The western blotting analysis was carried out to determine epithelial-mesenchymal transition (EMT) markers and AKT signaling. The interaction between MAPKAPK5-AS1, miR-154-5p, and PLAGL2 were explored by luciferase reporter assay and RNA immunoprecipitation. The regulatory effect of HIF-1α on MAPKAPK5-AS1 was evaluated by chromatin immunoprecipitation. Results MAPKAPK5-AS1 expression was significantly elevated in HCC, and its overexpression associated with malignant clinical features and reduced survival. Functionally, MAPKAPK5-AS1 knockdown repressed the proliferation, mobility, and EMT of HCC cells and induced apoptosis. Ectopic expression of MAPKAPK5-AS1 contributed to HCC cell proliferation and invasion in vitro. Furthermore, MAPKAPK5-AS1 silencing suppressed, while MAPKAPK5-AS1 overexpression enhanced HCC growth and lung metastasis in vivo. Mechanistically, MAPKAPK5-AS1 upregulated PLAG1 like zinc finger 2 (PLAGL2) expression by acting as an endogenous competing RNA (ceRNA) to sponge miR-154-5p, thereby activating EGFR/AKT signaling. Importantly, rescue experiments demonstrated that the miR-154-5p/PLAGL2 axis mediated the function of MAPKAPK5-AS1 in HCC cells. Interestingly, we found that hypoxia-inducible factor 1α (HIF-1α), a transcript factor, could directly bind to the promoter to activate MAPKAPK5-AS1 transcription. MAPKAPK5-AS1 regulated HIF-1α expression through PLAGL2 to form a hypoxia-mediated MAPKAPK5-AS1/PLAGL2/HIF-1α signaling loop in HCC. Conclusions Our results reveal a MAPKAPK5-AS1/PLAGL2/HIF-1α signaling loop in HCC progression and suggest that MAPKAPK5-AS1 could be a potential novel therapeutic target of HCC.

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Section: Introductionmentioning

confidence: 99%

Long non-coding RNA MAPKAPK5-AS1/PLAGL2/HIF-1α signaling loop promotes hepatocellular carcinoma progression

Wang

Sun

Liu

et al. 2021

J Exp Clin Cancer Res

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“…Numerous studies have indicated that lncRNAs are aberrantly expressed and serve as diagnostic and prognostic biomarkers in HCC (40)(41)(42). LncRNA DUXAP8, as an oncogene, is dysregulated in multiple tumors, such as bladder cancer ( 13), non-small-cell lung cancer (43) and ovarian cancer (44).…”

Section: Discussionmentioning

confidence: 99%

Long non‑coding RNA DUXAP8 promotes tumorigenesis by regulating IGF1R via miR‑9‑3p in hepatocellular carcinoma

et al. 2021

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Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide with a low 5-year survival rate. Long non-coding RNA (lncRNA) double homeobox A pseudogene 8 (DUXAP8) is an oncogene and a potential biomarker in various tumors, such as ovarian, colorectal and non-small-cell lung cancer. However, the function and molecular mechanism underlying DUXAP8 in HCC progression is not completely understood. The expression of DUXAP8, microRNA (miR)-9-3p and insulin-like growth factor 1 receptor (IGF1R) in HCC tissues and cells was detected via reverse transcription-quantitative PCR. The expression levels of IGF1R and epithelial-mesenchymal transition-associated proteins (Snail, Slug, E-cadherin, N-cadherin and vimentin) were assessed via western blotting. The effects of DUXAP8, miR-9-3p and IGF1R on proliferation, migration and invasion were examined by conducting Cell Counting Kit-8 and Transwell assays, respectively. The interaction between miR-9-3p and DUXAP8 or IGF1R was predicted using StarBase or TargetScan, and further assessed using dual luciferase reporter and RNA immunoprecipitation assays. DUXAP8 and IGF1R were upregulated and miR-9-3p was downregulated in HCC tissues and cells compared with adjacent healthy tissues and a normal liver cell line, respectively. miR-9-3p overexpression decreased the protein expression level of IGF1R, and miR-9-3p knockdown enhanced the protein expression level of IGF1R in HCC cells compared with the corresponding control groups. Moreover, compared with the corresponding control groups, DUXAP8 knockdown and miR-9-3p overexpression increased E-cadherin protein expression levels, and decreased Snail, Slug, N-cadherin and vimentin protein expression levels. However, miR-9-3p inhibitor and IGF1R overexpression reversed DUXAP8 knockdown-and miR-9-3p overexpression-induced effects, respectively. In addition, compared with the corresponding control groups, DUXAP8 knockdown and miR-9-3p overexpression suppressed proliferation, migration and invasion, which was reversed by miR-9-3p inhibitor and IGF1R overexpression, respectively. Moreover, miR-9-3p as the target of DUXAP8 and IGF1R as the target of miR-9-3p were verified in HCC cells. lncRNA DUXAP8 contributed to HCC tumorigenesis via the miR-9-3p/IGF1R axis, providing a novel therapeutic approach for HCC diagnosis and treatment.

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“…Interestingly, additional studies showed the existence of a large number of stable miRNAs in human serum/plasma, which laid the foundation for studying the role of serum/plasma microRNAs in the diagnosis and prognosis of HCC [80][81][82][83]. Differential expression of several serum microRNAs, including miR-16, miR122, miR-21, miR-223, miR-25, miR-375, and let-7f, in patients with HCC, patients with hepatitis B, and healthy individuals was reported recently [84][85][86][87].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-497-5p Is Downregulated in Hepatocellular Carcinoma and Associated with Tumorigenesis and Poor Prognosis in Patients

Jiang

Liu

et al. 2021

International Journal of Genomics

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Background. MicroRNAs (miRNAs) have been demonstrated to exhibit important regulatory roles in multiple malignancies, including hepatocellular carcinoma (HCC). hsa-miR-497-5p was reported to involve in cancer progression and poor prognosis in many kinds of tumors. However, the expression and its clinical significance of hsa-miR-497-5p in HCC remain unclear. Methods. In the present study, we investigated the expression of hsa-miR-497-5p in HCC and analyzed the correction of clinical features with prognosis. The expression levels of hsa-miR-497-5p and potential target genes were analyzed in HCC and adjacent noncancerous tissues using The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) datasets. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to analyze hsa-miR-497-5p levels in 328 HCC tissues and 30 paired adjacent noncancer tissues. Overall survival (OS) and progression-free survival (PFS) of patients with HCC were assessed using the Kaplan-Meier method and the log-rank test. Results. The hsa-miR-497-5p expression levels were decreased, and its target genes ACTG1, CSNK1D, PPP1CC, and BIRC5 were upregulated in HCC tissues compared with normal tissues. Lower levels of hsa-miR-497-5p expression and higher levels of the four target genes were significantly associated with higher tumor diameter. Moreover, patients with lower hsa-miR-497-5p expression and higher target genes levels had shorter OS. Conclusion. The expression levels of hsa-miR-497-5p may play an important regulatory role in HCC and are closely correlated with HCC progression and poor prognosis in patients. The hsa-miR-497-5p may be a specific therapeutic target for the treatment of HCC.

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

Cited by 68 publications

References 33 publications

Long non-coding RNA MAPKAPK5-AS1/PLAGL2/HIF-1α signaling loop promotes hepatocellular carcinoma progression

Long non-coding RNA MAPKAPK5-AS1/PLAGL2/HIF-1α signaling loop promotes hepatocellular carcinoma progression

Long non‑coding RNA DUXAP8 promotes tumorigenesis by regulating IGF1R via miR‑9‑3p in hepatocellular carcinoma

MicroRNA-497-5p Is Downregulated in Hepatocellular Carcinoma and Associated with Tumorigenesis and Poor Prognosis in Patients

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