The Role of miRNAs in Angiogenesis, Invasion and Metabolism and Their Therapeutic Implications in Gliomas

Beyer, Sasha; Fleming, Jessica L.; Wang, Meng; Singh, Rajbir; Haque, S. Jaharul; Chakravarti, Arnab

doi:10.3390/cancers9070085

Cited by 43 publications

(22 citation statements)

References 135 publications

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“…The development of glioma is a complex biological process that involves multiple mechanisms and factors (10,11). Numerous tumor suppressor genes, oncogenes, and growth factors have been confirmed to be involved in glioma progression (12)(13)(14). Recent studies have proven that other types of biomolecules, such as circular RNAs (circRNAs), also play essential roles in this process (15,16).…”

Section: Introductionmentioning

confidence: 99%

Lcn2-derived Circular RNA (hsa_circ_0088732) Inhibits Cell Apoptosis and Promotes EMT in Glioma via the miR-661/RAB3D Axis

Jin

Liu

et al. 2020

Front. Oncol.

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Background: Glioma is the most common malignant tumor of the central nervous system, and often displays invasive growth. Recently, circular RNA (circRNA), which is a novel non-coding type of RNA, has been shown to play a vital role in glioma tumorigenesis. However, the functions and mechanism of lipocalin-2 (Lcn2)-derived circular RNA (hsa_circ_0088732) in glioma progression remain unclear. Methods: We evaluated hsa_circ_0088732 expression by fluorescence in situ hybridization (FISH), Sanger sequencing, and PCR assays. Cell apoptosis was evaluated by flow cytometry and Hoechst 33258 staining. Transwell migration and invasion assays were performed to measure cell metastasis and viability. In addition, the target miRNA of hsa_circ_0088732 and the target gene of miR-661 were predicted by a bioinformatics analysis, and the interactions were verified by dual-luciferase reporter assays. RAB3D expression was analyzed by an immunochemistry assay, and E-cadherin, N-cadherin, and vimentin protein expression were examined by western blot assays. A mouse xenograft model was developed and used to analyze the effects of hsa_circ_0088732 on glioma growth in vivo. Results: We verified that hsa_circ_0088732 is circular and highly expressed in glioma tissues. Knockdown of hsa_circ_0088732 induced glioma cell apoptosis and inhibited glioma cell migration, invasion, and epithelial-mesenchymal transition (EMT). We found that hsa_circ_0088732 negatively regulated miR-661 by targeting miR-661, and RAB3D was a target gene of miR-661. In addition, inhibition of miR-661 promoted glioma cell metastasis and suppressed cell apoptosis. Knockdown of RAB3D induced cell apoptosis and suppressed cell metastasis. Moreover, hsa_circ_0088732 accelerated glioma progression through its effects on the miR-661/RAB3D axis. Finally, results from a mouse xenograft model confirmed that knockdown of hsa_circ_0088732 induced miR-661 expression, resulting in suppression of RAB3D expression and inhibition of tumor growth in vivo. Jin et al. hsa_circ_0088732 Acts as an Oncogene in Glioma Conclusion: We demonstrated that hsa_circ_0088732 facilitated glioma progression by sponging miR-661 to increase RAB3D expression. This study provides a theoretical basis for understanding the development and occurrence of glioma, as well as for the development of targeted drugs.

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Section: Introductionmentioning

confidence: 99%

Lcn2-derived Circular RNA (hsa_circ_0088732) Inhibits Cell Apoptosis and Promotes EMT in Glioma via the miR-661/RAB3D Axis

Jin

Liu

et al. 2020

Front. Oncol.

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“…[13][14][15] RNA interference (RNAi) knocks down SSRP1, inhibits tumour transformation and impairs tumour cell viability, but nontumour cells can tolerate this knockdown well. [19][20][21] Recently, an increasing number of studies have reported that miRNAs can regulate various cellular processes in cancer, such as proliferation, apoptosis, metastasis and chemoresistance. 17,18 These results imply that SSRP1 is a potential target in cancer therapy.…”

Section: Introductionmentioning

confidence: 99%

“…MicroRNAs (miRNAs) are small noncoding RNA molecules that are highly conserved and can induce mRNA cleavage or repress translation by targeting the 3'UTR of corresponding mRNAs. [19][20][21] Recently, an increasing number of studies have reported that miRNAs can regulate various cellular processes in cancer, such as proliferation, apoptosis, metastasis and chemoresistance. 20 In this study, we have been suggested that the abnormal expression of SSRP1 in CRC is partly due to the upstream dysregulation of miRNAs.…”

Section: Introductionmentioning

confidence: 99%

SSRP1 promotes colorectal cancer progression and is negatively regulated by miR‐28‐5p

Guo

et al. 2019

J Cellular Molecular Medi

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In this study, microarray data analysis, real‐time quantitative PCR and immunohistochemistry were used to detect the expression levels of SSRP1 in colorectal cancer (CRC) tissue and in corresponding normal tissue. The association between structure‐specific recognition protein 1 (SSRP1) expression and patient prognosis was examined by Kaplan‐Meier analysis. SSRP1 was knocked down and overexpressed in CRC cell lines, and its effects on proliferation, cell cycling, migration, invasion, cellular energy metabolism, apoptosis, chemotherapeutic drug sensitivity and cell phenotype‐related molecules were assessed. The growth of xenograft tumours in nude mice was also assessed. MiRNAs that potentially targeted SSRP1 were determined by bioinformatic analysis, Western blotting and luciferase reporter assays. We showed that SSRP1 mRNA levels were significantly increased in CRC tissue. We also confirmed that this upregulation was related to the terminal tumour stage in CRC patients, and high expression levels of SSRP1 predicted shorter disease‐free survival and faster relapse. We also found that SSRP1 modulated proliferation, metastasis, cellular energy metabolism and the epithelial‐mesenchymal transition in CRC. Furthermore, SSRP1 induced apoptosis and SSRP1 knockdown augmented the sensitivity of CRC cells to 5‐fluorouracil and cisplatin. Moreover, we explored the molecular mechanisms accounting for the dysregulation of SSRP1 in CRC and identified microRNA‐28‐5p (miR‐28‐5p) as a direct upstream regulator of SSRP1. We concluded that SSRP1 promotes CRC progression and is negatively regulated by miR‐28‐5p.

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“…To identify candidate miRNAs of increased therapeutic importance, both upregulated and downregulated miRNAs in primary and metastatic brain cancers were compared. Based on the existing literature, differentially expressed miRNAs in GBM [117][118][119][120][121][122][123][124][125][126][127][128][129] and BrM [130][131][132][133][134][135][136][137] were grouped, which resulted in four different groups, including GBM upregulated, GBM downregulated, BrM upregulated, and BrM downregulated. Venn diagram-based comparison of miRNAs was then performed to identify the putative miRNAs of therapeutic importance ( Figure 2 and Table 1), and differentially expressed miRNAs in both GBM and BrM are discussed in detail below.…”

Section: Mirnas Differentially Regulated In Brain Cancermentioning

confidence: 99%

Therapeutically Significant MicroRNAs in Primary and Metastatic Brain Malignancies

Akilandeswari

Larcher

Chen

et al. 2020

Cancers

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Brain cancer is one among the rare cancers with high mortality rate that affects both children and adults. The most aggressive form of primary brain tumor is glioblastoma. Secondary brain tumors most commonly metastasize from primary cancers of lung, breast, or melanoma. The five-year survival of primary and secondary brain tumors is 34% and 2.4%, respectively. Owing to poor prognosis, tumor heterogeneity, increased tumor relapse, and resistance to therapies, brain cancers have high mortality and poor survival rates compared to other cancers. Early diagnosis, effective targeted treatments, and improved prognosis have the potential to increase the survival rate of patients with primary and secondary brain malignancies. MicroRNAs (miRNAs) are short noncoding RNAs of approximately 18–22 nucleotides that play a significant role in the regulation of multiple genes. With growing interest in the development of miRNA-based therapeutics, it is crucial to understand the differential role of these miRNAs in the given cancer scenario. This review focuses on the differential expression of ten miRNAs (miR-145, miR-31, miR-451, miR-19a, miR-143, miR-125b, miR-328, miR-210, miR-146a, and miR-126) in glioblastoma and brain metastasis. These miRNAs are highly dysregulated in both primary and metastatic brain tumors, which necessitates a better understanding of their role in these cancers. In the context of the tumor microenvironment and the expression of different genes, these miRNAs possess both oncogenic and/or tumor-suppressive roles within the same cancer.

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The Role of miRNAs in Angiogenesis, Invasion and Metabolism and Their Therapeutic Implications in Gliomas

Cited by 43 publications

References 135 publications

Lcn2-derived Circular RNA (hsa_circ_0088732) Inhibits Cell Apoptosis and Promotes EMT in Glioma via the miR-661/RAB3D Axis

Lcn2-derived Circular RNA (hsa_circ_0088732) Inhibits Cell Apoptosis and Promotes EMT in Glioma via the miR-661/RAB3D Axis

SSRP1 promotes colorectal cancer progression and is negatively regulated by miR‐28‐5p

Therapeutically Significant MicroRNAs in Primary and Metastatic Brain Malignancies

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