MicroRNA-365 promotes lung carcinogenesis by downregulating the USP33/SLIT2/ROBO1 signalling pathway

Wang, Yuhuan; Zhang, Shuhua; Bao, Hejing; Mu, Shukun; Zhang, Baishen; Ma, Hao; Ma, Shudong

doi:10.1186/s12935-018-0563-6

Cited by 40 publications

(28 citation statements)

References 49 publications

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“…30 Slit2/ Robo1 signaling has been shown to suppress tumor cell proliferation and migration in lung carcinogenesis and the Slit/Robo1 axis is involved in cancer pathogenesis of esophageal squamous cell carcinoma by mediating cell invasion. 31,32 Furthermore, our study showed that the role of Robo1 silencing in HCC was achieved through inactivation of the PI3K/AKT/mTOR signaling pathway. Consistent to our results, a prior study suggested that Robo1 inhibits PI3K/AKT pathway to suppress angiogenesis in diabetic nephropathy.…”

Section: Discussionmentioning

confidence: 82%

Long non-coding RNA LINC00473 acts as a microRNA-29a-3p sponge to promote hepatocellular carcinoma development by activating Robo1-dependent PI3K/AKT/mTOR signaling pathway

Song

Zhang

et al. 2020

Ther Adv Med Oncol

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Background: Long non-coding RNAs have suppressive or oncogenic effects in various types of cancers by serving as competing endogenous RNAs for specific microRNAs. In the present study, we aim to delineate the underlying mechanism by which the LINC00473/miR-29a-3p/Robo1 axis affects cell proliferation, migration, invasion, and metastasis in hepatocellular carcinoma (HCC). Methods: The level of Robo1 was examined in HCC tissues and cells, along with its regulatory effects on proliferation, migration, and invasion of HCC cells. Afterwards, the possible involvement of the PI3K/AKT/mTOR signaling pathway was determined. Next, miR-29a-3p expression was overexpressed or inhibited to investigate its regulatory role on HCC cell activities. The interaction among miR-29a-3p, Robo1, and LINC00473 was further characterized. Finally, a xenograft tumor in nude mice was conducted to measure tumorigenesis and metastasis in vivo. Results: miR-29a-3p was downregulated while Robo1 was upregulated in HCC tissues and cells. miR-29a-3p targeted Robo1 and negatively regulated its expression. In response to miR-29a-3p overexpression, Robo1 silencing or LINC00473 silencing, HCC cell proliferation, migration, invasion, tumor progression, and metastasis were impeded, which was involved with the inactivation of the PI3K/AKT/mTOR signaling pathway. Notably, LINC00473 could competitively bind to miR-29a-3p to upregulate Robo1 expression. Conclusion: LINC00473 might be involved in HCC progression by acting as a miR-29a-3p sponge to upregulate the expression of Robo1 that activates the PI3K/AKT/mTOR signaling pathway, which leads to enhanced cell proliferation, migration, invasion, tumor progression, and metastasis in HCC.

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Section: Discussionmentioning

confidence: 82%

Long non-coding RNA LINC00473 acts as a microRNA-29a-3p sponge to promote hepatocellular carcinoma development by activating Robo1-dependent PI3K/AKT/mTOR signaling pathway

Song

Zhang

et al. 2020

Ther Adv Med Oncol

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“…Exosomal drug-efflux pumps and miRNAs can regulate anti-cancer drug resistance (100). miR-365a-3p enhance the migration and invasion of lung cancer cells by inhibiting ubiquitin specific peptidase 33 (USP33)/ slit guidance ligand 2 (SLIT2)/ roundabout guidance Receptor 1 (ROBO1) signaling pathway (101). Exosomal miR-365 from imatinib resistant chronic myeloid leukemia cells can confer drug resistance phenotypes in imatinib-sensitive chronic myeloid leukemia cells by decreasing apoptosis (102).…”

Section: Exosomal Mirnas Of Cancer Cells Regulate Anti-cancer Drug Rementioning

confidence: 99%

Exosomal MicroRNAs as Mediators of Cellular Interactions Between Cancer Cells and Macrophages

Kwon

Kim

et al. 2020

Front. Immunol.

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Tumor microenvironment consists of cancer cells and various stromal cells such as endothelial cells, cancer-associated fibroblasts (CAFs), myeloid-derived suppressor cells (MDSCs), neutrophils, macrophages, and other innate and adaptive immune cells. Of these innate immune cells, macrophages are an extremely heterogeneous population, and display both pro-inflammatory and anti-inflammatory functions. While M1 macrophages (classically activated macrophages) display anti-tumoral and pro-inflammatory functions, M2 macrophages display pro-tumoral and anti-inflammatory functions. Cellular interactions and molecular factors in the tumor microenvironment affect the polarization of macrophages. We review molecules and immune cells that influence the polarization status of macrophages. Tumor-associated macrophages (TAMs) generally express M2 phenotype, and mediate many processes that include tumor initiation, angiogenesis, and metastasis. A high number of TAMs has been associated with the poor prognosis of cancers. MicroRNAs (miRNAs) have been known to regulate cellular interactions that involve cancer cells and macrophages. Tumor-derived exosomes play critical roles in inducing the M1 or M2-like polarization of macrophages. The roles of exosomal miRNAs from tumor cells in the polarization of macrophages are also discussed and the targets of these miRNAs are presented. We review the effects of exosomal miRNAs from TAMs on cancer cell invasion, growth, and anti-cancer drug resistance. The relevance of exosomal microRNAs (miRNAs) as targets for the development of anti-cancer drugs is discussed. We review recent progress in the development of miRNA therapeutics aimed at elevating or decreasing levels of miRNAs.

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“…Scholars have defined microRNA (miRNA) as a small noncoding single‐stranded RNA that can bind to target genes, inhibiting the protein translation of the target genes or degrading the mRNA and thus regulating the expression of downstream target genes and their biological functions . Studies have shown that HIF‐1α can be the target gene of various miRNAs.…”

Section: Introductionmentioning

confidence: 99%

Expression significance and potential mechanism of hypoxia‐inducible factor 1 alpha in patients with myelodysplastic syndromes

Liang

Luo

et al. 2019

Cancer Medicine

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Objective To investigate the expression level and potential mechanism of hypoxia‐inducible factor 1 alpha (HIF‐1α) in patients with myelodysplastic syndromes (MDS). Methods Immunohistochemistry (IHC) techniques were used to examine the protein expression of HIF‐1α in paraffin‐embedded myeloid tissues from 82 patients with MDS and 33 controls (patients with lymphoma that is not invading myeloid tissues). In addition, the associations between the protein expression of HIF‐1α and clinical parameters were examined. To further investigate the significance of HIF‐1α expression in MDS patients, the researchers not only extracted the data about HIF‐1α expression from MDS‐related microarrays but also analyzed the correlation between the level of HIF‐1α expression and MDS. The microRNA (miRNA) targeting HIF‐1α was predicted and verified with a dual luciferase experiment. Results Immunohistochemistry revealed that the positive expression rate of HIF‐1α in the bone marrow of patients with MDS was 90.24%. This rate was remarkably higher than that of the controls (72.73%) and was statistically significant (P < .05), which indicated that HIF‐1α was upregulated in the myeloid tissues of MDS patients. For the GSE2779, GSE18366, GSE41130, and GSE61853 microarrays, the average expression of HIF‐1α in MDS patients was higher than in the controls. Particularly for the GSE18366 microarray, HIF‐1α expression was considerably higher in MDS patients than in the controls (P < .05). It was predicted that miR‐93‐5p had a site for binding with HIF‐1α, and a dual luciferase experiment confirmed that miR‐93‐5p could bind with HIF‐1α. Conclusion The upregulated expression of HIF‐1α was examined in the myeloid tissues of MDS patients. The presence of HIF‐1α (+) suggested an unsatisfactory prognosis for patients, which could assist in the diagnosis of MDS. In addition, miR‐93‐5p could bind to HIF‐1α by targeting, showing its potential to be the target of HIF‐1α in MDS.

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MicroRNA-365 promotes lung carcinogenesis by downregulating the USP33/SLIT2/ROBO1 signalling pathway

Cited by 40 publications

References 49 publications

Long non-coding RNA LINC00473 acts as a microRNA-29a-3p sponge to promote hepatocellular carcinoma development by activating Robo1-dependent PI3K/AKT/mTOR signaling pathway

Long non-coding RNA LINC00473 acts as a microRNA-29a-3p sponge to promote hepatocellular carcinoma development by activating Robo1-dependent PI3K/AKT/mTOR signaling pathway

Exosomal MicroRNAs as Mediators of Cellular Interactions Between Cancer Cells and Macrophages

Expression significance and potential mechanism of hypoxia‐inducible factor 1 alpha in patients with myelodysplastic syndromes

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