miR-199a-3p/5p regulate tumorgenesis via targeting Rheb in non-small cell lung cancer

Liu, Xiaomin; Wang, Xianyi; Chai, Binshu; Wu, Zong; Gu, Zhenyu; Zou, Heng; Zhang, Hui; Li, Yanli; Sun, Qiangling; Fang, Wentao

doi:10.7150/ijbs.70312

Cited by 12 publications

(9 citation statements)

References 47 publications

(46 reference statements)

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“…In addition, the increased expression level of miR-199a-5p could inhibit the proliferation of lung cancer cells and arrest the cell cycle in the G1 phase. In another of our research papers [ 37 ], we found that miR-199a-3p/5p were down-expressed in NSCLC tissue samples, cell lines, and the patient sample database. miR-199a-3p/5p overexpression could significantly suppress cell proliferation, migration ability and promote apoptosis.…”

Section: Resultsmentioning

confidence: 99%

“…Some of the identified target genes of miR-199a may also be the targets of future drugs. For example, as mentioned above, our lab studies found that miR-199a-3p and miR-199a-5p could directly co-target Rheb (Ras homolog enriched in the brain) in lung cancer [ 37 ], regulating the mTOR signaling pathway, inhibiting cell proliferation, migration, and promoting cell apoptosis. The same is true for our laboratory’s discovery of MAP3K11 as a target gene for miR-199a-5p in NSCLC [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

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miR-199a: A Tumor Suppressor with Noncoding RNA Network and Therapeutic Candidate in Lung Cancer

Wei

Chai

et al. 2022

IJMS

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Lung cancer is the leading cause of cancer death worldwide. miR-199a, which has two mature molecules: miR-199a-3p and miR-199a-5p, plays an important biological role in the genesis and development of tumors. We collected recent research results on lung cancer and miR-199a from Google Scholar and PubMed databases. The biological functions of miR-199a in lung cancer are reviewed in detail, and its potential roles in lung cancer diagnosis and treatment are discussed. With miR-199a as the core point and a divergence outward, the interplay between miR-199a and other ncRNAs is reviewed, and a regulatory network covering various cancers is depicted, which can help us to better understand the mechanism of cancer occurrence and provide a means for developing novel therapeutic strategies. In addition, the current methods of diagnosis and treatment of lung cancer are reviewed. Finally, a conclusion was drawn: miR-199a inhibits the development of lung cancer, especially by inhibiting the proliferation, infiltration, and migration of lung cancer cells, inhibiting tumor angiogenesis, increasing the apoptosis of lung cancer cells, and affecting the drug resistance of lung cancer cells. This review aims to provide new insights into lung cancer therapy and prevention.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

miR-199a: A Tumor Suppressor with Noncoding RNA Network and Therapeutic Candidate in Lung Cancer

Wei

Chai

et al. 2022

IJMS

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“…Among the above-mentioned miRNAs closely related to liver cancer, we selected miR-199a-3p, which was upregulated in the ATXP group vs. the model group and had the smallest differential expression, as the research object for follow-up experiments. miR-199a-3p had been identified in recent years as a promising diagnostic biomarker in a variety of malignancies, such as liver cancer, colorectal cancer ( 59 ), lung cancer ( 60 ), esophageal cancer ( 61 ), and ovarian cancer ( 62 ). The study found that miR-199a-3p was underexpressed in liver cancer, which was in line with our sequencing results.…”

Section: Discussionmentioning

confidence: 99%

The intervention effect of Aitongxiao prescription on primary liver cancer rats was evaluated based on high-throughput miRNA sequencing and bioinformatics analysis

Cheng

et al. 2023

Front. Oncol.

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Liver cancer is a common malignant tumor known for its difficult treatment and poor prognosis. As a traditional Chinese medicine prescription, Aitongxiao prescription (ATXP) has been used in clinical treatment of primary liver cancer (PLC) for more than ten years, and its therapeutic effect is obvious and has been verified over time. However, the mechanism of ATXP in treating PLC has not been fully elucidated. This study aimed to detect the liver-protective effect of ATXP on a PLC rat model and explore its potential mechanism from the perspective of plasma extracellular vesicle miRNAs. Fifty SPF male SD rats were randomly selected, with six rats as the control group, and the remaining rats were injected with DEN to establish a primary liver cancer model. The model rats were randomly divided into the model group and the ATXP group. After 4 weeks of intervention, the liver-protective effect of ATXP was evaluated using plasma biochemical indicators and histopathological methods. Plasma extracellular vesicles were isolated and extracted, and identified by transmission electron microscopy, nanoparticle tracking analysis, and western blot. Significant differentially expressed miRNAs in extracellular vesicles were screened by Illumina sequencing to explore the therapeutic targets of ATXP and conduct functional analysis. The results showed that ATXP significantly reduced plasma liver function in PLC rats and alleviated liver pathological damage. In addition, plasma extracellular vesicles were isolated and identified. According to the results of GO and KEGG analysis, they were related to multiple biological processes and covered multiple signaling pathways (PI3K-Akt and MAPK signaling pathways, etc.). The interaction between miR-199a-3p and MAP3K4 was determined by bioinformatics methods and dual-luciferase reporter gene detection, confirming that MAP3K4 is the target gene of miR-199a-3p. In conclusion, ATXP protects the liver from DEN-induced PLC, which may be related to the regulation of plasma extracellular vesicle miR-199a-3p. This study further reveals the mechanism of ATXP in treating liver cancer and provides a theoretical basis for subsequent research.

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“…MiR-155-5p suppresses the migration and invasion of lung adenocarcinoma cells by targeting Smad2 [ 39 ]. MiR-199a-5p suppresses NSCLC progression [ 40 ], while miR-200b-3p and miR-9 promote NSCLC metastasis by targeting ABCA1 and TGFBR2, respectively [ 41 , 42 ]. In the study, most of the selected miRNAs were upregulated in the PD-L1-transfected cells.…”

Section: Discussionmentioning

confidence: 99%

Tumor-Intrinsic PD-L1 Exerts an Oncogenic Function through the Activation of the Wnt/β-Catenin Pathway in Human Non-Small Cell Lung Cancer

Marinkova²,

Nenkov³

et al. 2022

IJMS

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Programmed death ligand 1 (PD-L1) strongly inhibits T cell activation, thereby aiding tumors in escaping the immune response. PD-L1 inhibitors have proven to be effective in the treatment of different types of cancer, including non-small cell lung cancer (NSCLC). Yet, the knowledge regarding the biological function of tumor-intrinsic PD-L1 in lung cancer remains obscure. In our study, we set the goal of determining the function of PD-L1 using overexpression and knockdown strategies. PD-L1 silencing resulted in decreased migratory and invasive ability of tumor cells, together with attenuated colony-forming capacity. Ectopic expression of PD-L1 showed the opposite effects, along with increased activities of MAPK and Wnt/β-catenin pathways, and the upregulation of Wnt/β-catenin target genes. Additionally, overexpression of PD-L1 was associated with dysregulated cellular and exosomal miRNAs involved in tumor progression and metastasis. In primary lung tumors, immunohistochemistry revealed that both PD1 and PD-L1 were highly expressed in squamous cell carcinoma (SCC) compared to adenocarcinoma (p = 0.045 and p = 0.036, respectively). In SCC, PD1 expression was significantly associated with tumor grading (p = 0.016). Taken together, our data suggest that PD-L1 may exert an oncogenic function in NSCLC through activating Wnt/β-catenin signaling, and may act as a potential diagnostic marker for lung SCC.

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miR-199a-3p/5p regulate tumorgenesis via targeting Rheb in non-small cell lung cancer

Cited by 12 publications

References 47 publications

miR-199a: A Tumor Suppressor with Noncoding RNA Network and Therapeutic Candidate in Lung Cancer

miR-199a: A Tumor Suppressor with Noncoding RNA Network and Therapeutic Candidate in Lung Cancer

The intervention effect of Aitongxiao prescription on primary liver cancer rats was evaluated based on high-throughput miRNA sequencing and bioinformatics analysis

Tumor-Intrinsic PD-L1 Exerts an Oncogenic Function through the Activation of the Wnt/β-Catenin Pathway in Human Non-Small Cell Lung Cancer

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