Long noncoding RNA DNAH17-AS1 promotes tumorigenesis and metastasis of non-small cell lung cancer via regulating miR-877–5p/CCNA2 pathway

Du, Liuying; Mao, Long-jun; Jing, Ruijun

doi:10.1016/j.bbrc.2020.09.047

Cited by 22 publications

(19 citation statements)

References 36 publications

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“…Hsa-miR-877 was found to be overexpressed in gastric cancer, and also antagonized the promoting effect of Substance P in the occurrence and progression of gastric cancer, suggesting that miR-877-5p could be a potential drug target [47] . Further, miR-877-5 has been reported to participate in gene regulation of competing endogenous RNA (ceRNA) mechanisms in multiple tumors, including cervical cancer, malignant gliomas, and non-small-cell lung cancer [48][49][50] . Yijun Yang et al showed that Hsa-miR-137 effectively induced apoptosis and diminished tumorigenicity in multiple myeloma [51] .…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Immune-infiltration Related miRNAs that can Predict the Prognosis of Patients with Hepatocellular Carcinoma

Liu

2022

Preprint

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Background: Although immune checkpoint inhibitors (ICIs) have achieved important breakthroughs in the treatment of liver cancer, most hepatocellular carcinoma (HCC) patients do not respond to ICIs, and their clinical outcome remains unsatisfactory. The tumor microenvironment (TME), which contains immune cells and other molecules, probably influences both the prognosis and the response to immunotherapy in HCC. Here, using integrated bioinformatics analyses, we identified key molecules (immune cells and immune-related microRNAs (miRNAs)) as potential prognostic markers for HCC.Method: MRNA and miRNA expression profiles and clinicopathological data were extracted from the Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) data collection. A total of 22 immune cell types from HCC patients were assessed using a deconvolution algorithm (known as CIBERSORT). Both Kaplan-Meier analysis and Cox proportional hazards regression were used to evaluate the prognostic value of the immunocytes. The correlations between differentially expressed miRNAs and tumor-infiltrating immune cells were investigated using the Pearson correlation coefficient. Machine learning approaches were employed to identify prognostic miRNAs. The miRTarBase database was used to construct a DEmiRNA-target gene network. Function enrichment analyses were performed using Metascape software. The relationships between two specific miRNAs and the expression of immune markers (antigen presenting machinery (APM) and tumor-infiltrating lymphocytes (TILs)) as well as cell checkpoint markers were also analyzed.Results: A total of 19 T regulatory cell (Treg)-related miRNAs were identified by machine learning approaches (p<0.001, |cor|>0.2). Metascape revealed that Treg-related miRNA-target networks were significantly enriched in biological processes including cellular responses to stress, mitotic cell cycle and myeloid cell differentiation. Using univariate Cox regression analysis on an independent dataset, GSE31384, 19 miRNAs were evaluated for their importance in overall survival (OS). Two hub miRNAs (hsa-miR-877 and hsa-miR-137) were found to significantly impact on OS. Therefore, we assessed the association between these two miRNAs and immune markers (APM, TILs) and cell checkpoint markers (programmed cell death-1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte antigen-4 (CTLA-4), B- and T-lymphocyte attenuator (BTLA)), and found statistically significant associations in both the TCGA and GSE31384 datasets.Conclusion: Our study showed that hsa-miR-877 and hsa-miR-137 were significantly associated with poor prognosis in HCC through their effects on Tregs and immune checkpoint markers in the TME. These results suggest that hsa-miR-877 and hsa-miR-137 might serve as novel therapeutic targets for HCC.

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Section: Discussionmentioning

confidence: 99%

Identification of Novel Immune-infiltration Related miRNAs that can Predict the Prognosis of Patients with Hepatocellular Carcinoma

Liu

2022

Preprint

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“…Continuing advances in the development of next-generation sequencing and transcriptomics suggest that the investigation of lncRNAs in the regulation of cancer has emerged as a potential research field [ 21 ]. Accumulating evidence shows that lncRNAs are involved in tumorigenesis and have the potential to be used as diagnostic and prognostic biomarker in a wide range of cancers [ 22 , 23 ]. Worldwide research has focused on identifying potential diagnostic and prognostic markers, which might predict survival outcomes accurately.…”

Section: Discussionmentioning

confidence: 99%

Muscleblind-like 1 antisense RNA 1 inhibits cell proliferation, invasion, and migration of prostate cancer by sponging miR-181a-5p and regulating PTEN/PI3K/AKT/mTOR signaling

Ding

et al. 2021

Bioengineered

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The present study aimed to investigate the role and underlying mechanisms of long non-coding RNA (lncRNA) muscleblind-like 1 antisense RNA 1 (MBNL1-AS1) in the progression of Prostate cancer (PCa). MBNL1-AS1 and microRNA (miR)-181a-5p expression in PCa tissues and several human PCa cell lines were analyzed, respectively, using StarBasev3.0 project and RT-qPCR assay. After MBNL1-AS1 overexpression, cell proliferation, invasion and migration were, respectively, evaluated using CCK-8, colony formation, transwell and wound healing assays. Dual luciferase assay were used for analysis of the interactions among MBNL1-AS1, miR-181a-5p, and phosphatase and tensin homolog (PTEN). Subsequently, the expression of PTEN and proteins in PI3K/AKT/mTOR signaling was examined using western blot analysis after transfection with miR-181a-5p mimic. The rescue assays were performed to investigate the effects of MBNL1-AS1 and miR-181a-5p on the functions of PCa cells and the expression of PTEN/PI3K/AKT/mTOR signaling by co-transfection with MBNL1-AS1 plasmid and miR-181a-5p mimic. Results indicated that MBNL1-AS1 was conspicuously downregulated while miR-181a-5p upregulating in PCa tissues and cell lines. MBNL1-AS1 overexpression decreased the abilities of cell proliferation, invasion, and migration. Further study revealed that MBNL1-AS1 acted as a sponge for miR-181a-5p and positively regulated PTEN by a sponge effect. Additionally, rescue assays proved that the effect of MBNL1-AS1-upregulation on the proliferation, invasion, and migration of PCa cells was dependent on miR-181a-5p. Furthermore, miR-181a-5p overexpression counteracted the expression of PTEN and proteins in PI3K/AKT/mTOR signaling exerted by MBNL1-AS1-upregulation in PCa cells. This study suggests that MBNL1-AS1 inhibits the progression of PCa via sponging miR-181a-5p and regulating PTEN/PI3K/AKT/mTOR pathway.

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“…14 On the contrary, miR-761 acted as a promoter in NSCLC cell malignancy by regulating cell proliferation and aggressiveness. 15 Given the feasibility of the circRNA-miRNA-mRNA regulatory network in revealing the mechanism responsible for cancer progression, 16,17 we predicted the miRNA and mRNA associated with circPRH1-PRR4 through bioinformatics tools. As a result, we found miR-877-5p was able to bind to circPRH1-PRR4, and the member RAS oncogene family (RAB3D) carried the complementary sites of miR-877-5p.…”

Section: Introductionmentioning

confidence: 99%

CircRNA PRH1‐PRR4 stimulates RAB3D to regulate the malignant progression of NSCLC by sponging miR‐877‐5p

2022

Thoracic Cancer

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Background: Previous reports have confirmed the importance of circular RNA (circRNA) in the malignant progression of non-small-cell lung cancer (NSCLC). However, the role of circRNA PRH1-PRR4 readthrough (circPRH1-PRR4) in NSCLC progression was unclear. This study was designed to reveal the mechanism behind circPRH1-PRR4 regulating NSCLC progression. Methods: Quantitative real-time polymerase chain reaction and western blot were employed to detect the expression of circPRH1-PRR4, microRNA-877-5p (miR-877-5p), the member RAS oncogene family (RAB3D), and other indicated protein markers. The positive expression rate of RAB3D was detected by immunohistochemistry assay. Cell proliferation was investigated by cell colony formation and 5-ethynyl-2 0 -deoxyuridine assays. Flow cytometry was employed to quantify apoptotic cells. Wound-healing and transwell invasion assays were used to evaluate cell metastasis. The interaction among circPRH1-PRR4, miR-877-5p, and RAB3D was identified by dual-luciferase reporter assay. In vivo assay was implemented to demonstrate the effect of circPRH1-PRR4 on tumor formation. Results: As compared with controls, NSCLC tissues and cells displayed high expression of circPRH1-PRR4 and RAB3D, and low expression of miR-877-5p. Reduced expression of circPRH1-PRR4 resulted in inhibition of cell proliferation, migration, and invasion, but promotion of cell apoptosis in vitro. In support, circPRH1-PRR4 silencing inhibited tumor formation in vivo. Knockdown of miR-877-5p, a target miRNA of circPRH1-PRR4, relieved circPRH1-PRR4 absence-mediated action. Additionally, RAB3D was identified as a target mRNA of miR-877-5p. Importantly, circPRH1-PRR4 regulated RAB3D expression by miR-877-5p. Conclusion: CircPRH1-PRR4 knockdown impeded NSCLC cell malignancy by the miR-877-5p/RAB3D pathway, providing a possible circRNA-targeted therapy for NSCLC.

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Long noncoding RNA DNAH17-AS1 promotes tumorigenesis and metastasis of non-small cell lung cancer via regulating miR-877–5p/CCNA2 pathway

Cited by 22 publications

References 36 publications

Identification of Novel Immune-infiltration Related miRNAs that can Predict the Prognosis of Patients with Hepatocellular Carcinoma

Identification of Novel Immune-infiltration Related miRNAs that can Predict the Prognosis of Patients with Hepatocellular Carcinoma

Muscleblind-like 1 antisense RNA 1 inhibits cell proliferation, invasion, and migration of prostate cancer by sponging miR-181a-5p and regulating PTEN/PI3K/AKT/mTOR signaling

CircRNA PRH1‐PRR4 stimulates RAB3D to regulate the malignant progression of NSCLC by sponging miR‐877‐5p

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