MicroRNA-224 promotes tumor progression in nonsmall cell lung cancer

Cui, Ri; Wang, Meng; Sun, Hui; Kim, Taewan; Ye, Zhenqing; Fassan, Matteo; Jeon, Young-Jun; Li, Bin; Vicentini, Caterina; Peng, Yong; Lee, Tae Jin; Luo, Zhenghua; Liu, Lan; Xu, Dongmei; Tili, Esmerina; Jin, Victor X.; Middleton, Justin; Chakravarti, Arnab; Lautenschlaeger, Tim; Croce, Carlo M.

doi:10.1073/pnas.1502068112

Cited by 130 publications

(133 citation statements)

References 45 publications

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“…In 2014, Zhu et al (19) reported that miR-224 was significantly downregulated in NSCLC and that a decrease in miR-224 expression was significantly associated with shorter OS time (19). Also in NSCLC, Cui et al (33) identified that miR-224 was significantly upregulated, with the increased expression of miR-224 promoting cell migration, invasion, and proliferation. As aforementioned, the present study also identified that the high expression levels of miR-224 were associated with shorter OS time in one subgroup of patients, specifically those who underwent chemotherapy combined with radiotherapy.…”

Section: Below Cut-offmentioning

confidence: 99%

Predictive relevance of miR‑34a, miR‑224 and miR‑342 in patients with advanced squamous cell carcinoma of the lung undergoing palliative chemotherapy

et al. 2017

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Abstract. Attributing to their pathophysiological role and stability in biological samples, microRNAs (miRNAs) have the potential to become valuable predictive markers for non-small cell lung cancer (NSCLC). Samples of biopsy tissue constitute suitable material for miRNA profiling with the aim of predicting the effect of palliative chemotherapy. The present study group included 81 patients (74 males, 7 females, all smokers or former smokers) with the squamous cell carcinoma (SCC) histological subtype of NSCLC at a late stage (3B or 4). All patients received palliative chemotherapy based on platinum derivatives in combination with paclitaxel or gemcitabine. The expression of 17 selected miRNAs was measured by reverse transcription-quantitative polymerase chain reaction in tumor tissue macrodissected from formalin-fixed paraffin-embedded (FFPE) tissue samples. To predict the effect of palliative chemotherapy, the association between gene expression levels and overall survival (OS) time was analyzed. From the 17 miRNAs of interest, low expression levels of miR-342 and high expression levels of miR-34a and miR-224 were associated with a reduced OS time in subgroups of patients based on smoking status and treatment modality. Using cluster analysis, associations between combinations of miR-34a, -224 and -342 expression levels with patient survival were identified. The present study revealed that patients with the simultaneous high expression of miR-224 and -342 had a similar prognostic outcome to those with the low expression of miR-224 and -342, which was significantly reduced, compared with patients exhibiting high expression of either miR-224 or miR-342 with low expression of the other. We hypothesize that the effect of a particular miRNA is dependent on the expression level of other members of the miRNA network. This finding appears to complicate survival analyses based on individual miRNAs as markers. In conclusion, the present study provides evidence that specific miRNAs were associated with OS time, which may be candidate predictors for the effectiveness of palliative treatment in SCC lung cancer patients. This objective can be better achieved by combining more markers together than by using individual miRNAs.

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Section: Below Cut-offmentioning

confidence: 99%

Predictive relevance of miR‑34a, miR‑224 and miR‑342 in patients with advanced squamous cell carcinoma of the lung undergoing palliative chemotherapy

et al. 2017

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“…Up-regulated mir-224 facilitates tumour progression by shifting the equilibrium of the partially antagonist functions of TNFaip1 and smad4 to enhanced invasion and growth in Nsclc (ref. 92 ). it has been reported that TNFaip1 stimulates dNa polymerase delta activity in vitro, suggesting that TNFaip1 might be involved in dNa synthesis and apoptosis 92,93 .…”

Section: Mirnas Involved In Lymph Node Metastasismentioning

confidence: 99%

“…92 ). it has been reported that TNFaip1 stimulates dNa polymerase delta activity in vitro, suggesting that TNFaip1 might be involved in dNa synthesis and apoptosis 92,93 . smad4 mediates TGF-beta signal transduction 94 .…”

Section: Mirnas Involved In Lymph Node Metastasismentioning

confidence: 99%

The role of microRNA in metastatic processes of non-small cell lung carcinoma

Pastorkova¹,

Škarda²,

Andel³

2016

BIOMED PAP

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Background. MicroRNAs are small non-coding one-stranded RNA molecules that play an important role in the posttranscriptional regulation of genes. Bioinformatic predictions indicate that each miRNA can regulate hundreds of target genes. MicroRNA expression can be associated with various cellular processes leading to the metastasis of malignant tumours including non-small cell lung carcinoma. This review summarizes current knowledge on the role of microRNAs in NSCLC metastasis to the brain and lymph nodes. Methods. A search of the NCBI/PubMed database for publications on expression levels and the mechanisms of microRNA action in NSCLC metastasis. Results and Conclusion. Dysregulation of microRNAs in NSCLC can be associated with brain and lymph node metastasis. There are differences in microRNA expression profiling between NSCLC with and without metastases but it is currently not possible to reliably predict the site of metastasis in NSCLC. Based on data from RNAmicroarrays, bioinformatics analysis is able to predict the target genes of highlighted microRNAs, providing us with complex information about cancer cell features such as enhanced proliferation, migration and invasion. Such microRNAs may then be knocked-down using siRNAs or substituted with miRNA mimics. RNA microarray profiling may thus be a useful tool to select up-or down-regulated microRNAs. A number of authors suggest that microRNAs could serve as biomarkers and therapeutic targets in the treatment of NSCLC metastasis.

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“…1 Despite advancements and improvements in surgical and medical treatments, the survival rate of lung cancer patients remains frustratingly poor. Local control for early-stage non-small-cell lung cancer (NSCLC) has dramatically improved over the last decades for both operable and inoperable patients, [2][3][4] but metastasis is still a major factor contributing to the high mortality of lung cancer. According to the World Health Organization (WHO), lung cancer will cause about 2.5 million deaths per year by the year 2030.…”

Section: Introductionmentioning

confidence: 99%

A herpes simplex virus type 2–encoded microRNA promotes tumor cell metastasis by targeting suppressor of cytokine signaling 2 in lung cancer

et al. 2017

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Certain viruses use microRNAs to regulate the expression of their own genes, host genes, or both. A number of microRNAs expressed by herpes simplex virus type 2 have been confirmed by previous studies. However, whether these microRNAs play a role in the metastasis of lung cancers and how these viral microRNAs precisely regulated the tumor biological process in lung cancer bone metastasis remain obscure. We recently identified the high expression of an acutely and latently expressed viral microRNA, Hsv2-miR-H9-5p, encoded by herpes simplex virus type 2 latencyassociated transcript through microarray and quantitative polymerase chain reaction analyses which compared the expression of microRNAs in bone metastasis from lung cancer with primary lung cancers. We now reported that Hsv2-miR-H9-5p was highly expressed in bone metastasis and closely associated with pathological and metastatic processes of lung cancers. The functions of Hsv2-miR-H9-5p were determined by overexpression which results in an increase in survival, migration, and invasion of lung cancer cells in vitro. We determined that Hsv2-miR-H9-5p directly targeted SOCS2 mechanistically by dual-luciferase reporter assay. Then, we investigated the functions of SOCS2 in the progress of lung cancers. Reduction of SOCS2 dosage by hsv2-miR-H9-5p induced increased migration and invasion of lung cancer cells. Overexpression of SOCS2 inverted these phenotypes generated by hsv2-miR-H9-5p, indicating the potential roles of SOCS2 in Hsv2-miR-H9-5p-driven metastasis in lung cancers. The results highlighted that Hsv2-miR-H9-5p regulated and contributed to bone metastasis of lung cancers. We proposed that Hsv2-miR-H9-5p could be used as a potential target in lung cancer therapy.

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MicroRNA-224 promotes tumor progression in nonsmall cell lung cancer

Cited by 130 publications

References 45 publications

Predictive relevance of miR‑34a, miR‑224 and miR‑342 in patients with advanced squamous cell carcinoma of the lung undergoing palliative chemotherapy

Predictive relevance of miR‑34a, miR‑224 and miR‑342 in patients with advanced squamous cell carcinoma of the lung undergoing palliative chemotherapy

The role of microRNA in metastatic processes of non-small cell lung carcinoma

A herpes simplex virus type 2–encoded microRNA promotes tumor cell metastasis by targeting suppressor of cytokine signaling 2 in lung cancer

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