Chemotherapy-Regulated microRNA-125–HER2 Pathway as a Novel Therapeutic Target for Trastuzumab-Mediated Cellular Cytotoxicity in Small Cell Lung Cancer

Yagishita, Shigehiro; Fujita, Yu; Kitazono, Satoru; Ko, Ryo; Nakadate, Yusuke; Sawada, Takeshi; Kitamura, Yuka; Shimoyama, Tatsu; Maeda, Yoshiharu; Takahashi, Fumiyuki; Takahashi, Kazuhisa; Tamura, Tomohide; Koizumi, Fumiaki

doi:10.1158/1535-7163.mct-14-0625

Cited by 24 publications

(18 citation statements)

References 34 publications

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“…Our study showed that no miRNA was different between males and females in adenoma-free mice, while 3 miRNAs (miR-10a, miR-125, and miR-130a) were differentially expressed in adenoma-bearing male and female mice. In particular, miR-10a is related to estrogen dependent cancer promotion [112, 113], miR-130a both to the estrogen and HER2 pathways [114, 115], and miR-125 to HER2/erbb2 estrogen sensitive oncogene activation [116, 117]. These findings support the view that estrogen and HER2-dependent mechanisms can contribute to CS-induced lung carcinogenicity in females.…”

Section: Discussionmentioning

confidence: 62%

Blood and lung microRNAs as biomarkers of pulmonary tumorigenesis in cigarette smoke-exposed mice

Izzotti

Balansky²,

Ganchev³

et al. 2016

Oncotarget

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Cigarette smoke (CS) is known to dysregulate microRNA expression profiles in the lungs of mice, rats, and humans, thereby modulating several pathways involved in lung carcinogenesis and other CS-related diseases. We designed a study aimed at evaluating (a) the expression of 1135 microRNAs in the lung of Swiss H mice exposed to mainstream CS during the first 4 months of life and thereafter kept in filtered air for an additional 3.5 months, (b) the relationship between lung microRNA profiles and histopathological alterations in the lung, (c) intergender differences in microRNA expression, and (d) the comparison with microRNA profiles in blood serum. CS caused multiple histopathological alterations in the lung, which were almost absent in sham-exposed mice. An extensive microRNA dysregulation was detected in the lung of CS-exposed mice. Modulation of microRNA profiles was specifically related to the histopathological picture, no effect being detected in lung fragments with non-neoplastic lung diseases (emphysema or alveolar epithelial hyperplasia), whereas a close association occurred with the presence and multiplicity of preneoplastic lesions (microadenomas) and benign lung tumors (adenomas). Three microRNAs regulating estrogen and HER2-dependent mechanisms were modulated in the lung of adenoma-bearing female mice. Blood microRNAs were also modulated in mice affected by early neoplastic lesions. However, there was a poor association between lung microRNAs and circulating microRNAs, which can be ascribed to an impaired release of mature microRNAs from the damaged lung. Studies in progress are evaluating the feasibility of analyzing blood microRNAs as a molecular tool for lung cancer secondary prevention.

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Section: Discussionmentioning

confidence: 62%

Blood and lung microRNAs as biomarkers of pulmonary tumorigenesis in cigarette smoke-exposed mice

Izzotti

Balansky²,

Ganchev³

et al. 2016

Oncotarget

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“…MiR-125b was selected and validated in vitro using UACC-812 cell (Additional file 13: Figure S2f, g). It was reported that ERBB2 was a target of MiR-125b in solid cancers [41, 48, 49]. Thus, expression of MiR-125b and ERBB2 in breast cancer was investigated.…”

Section: Resultsmentioning

confidence: 99%

Oncogenic long noncoding RNA landscape in breast cancer

et al. 2017

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BackgroundFew long noncoding RNAs (lncRNAs) that act as oncogenic genes in breast cancer have been identified.MethodsOncogenic lncRNAs associated with tumourigenesis and worse survival outcomes were examined and validated in Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), respectively. Then, the potential biological functions and expression regulation of these lncRNAs were studied via bioinformatics and genome data analysis. Moreover, progressive breast cancer subtype-specific lncRNAs were investigated via high-throughput sequencing in our cohort and TCGA validation. To elucidate the mechanisms of the regulation of these lncRNAs, genomic alterations from the TCGA, Broad, Sanger and BCCRC data, as well as epigenetic modifications from GEO data, were then applied and examined to meet this objective. Finally, cell proliferation assays, flow cytometry analyses and TUNEL assays were applied to validate the oncogenic roles of these lncRNAs in vitro.ResultsA cluster of oncogenic lncRNAs that was upregulated in breast cancer tissue and was associated with worse survival outcomes was identified. These oncogenic lncRNAs are involved in regulating immune system activation and the TGF-beta and Jak-STAT signalling pathways. Moreover, TINCR, LINC00511, and PPP1R26-AS1 were identified as subtype-specific lncRNAs associated with HER-2, triple-negative and luminal B subtypes of breast cancer, respectively. The up-regulation of these oncogenic lncRNAs is mainly caused by gene amplification in the genome in breast cancer and other solid tumours. Finally, the knockdown of TINCR, DSCAM-AS1 or HOTAIR inhibited breast cancer cell proliferation, increased apoptosis and inhibited cell cycle progression in vitro.ConclusionsThese findings enhance the landscape of known oncogenic lncRNAs in breast cancer and provide insights into their roles. This understanding may potentially aid in the comprehensive management of breast cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-017-0696-6) contains supplementary material, which is available to authorized users.

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“…In striking contrast, endometrial cancer tissue samples showed a significant decrease in fourteen tumor-suppressive miRNAs (Figure 1C). It is of interest to note here that all of the fourteen downregulated miRNAs, namely, miR-26a-5p [22, 23], miR-150-5p [24, 25], let-7f-5p [26, 27], miR-26b-5p [22, 23, 28], let-7c-5p [26, 27], miR-23b-5p [29-31], miR-126-3p [32], miR-125b-5p [33], hsa-miR-195-5p [34, 35], miR-424-5p [36, 37], hsa-miR-374a-5p [38-40], let-7a-5p [26, 27] , let-7e-5p [26, 27], and miR-125a-5p [41, 42] are known to have tumor-suppressive function in many cancers. Taken together with the upregulated genes, our results identify a panel of miRNAs that correlates with the tumor phenotype.…”

Section: Resultsmentioning

confidence: 99%

Identification of novel diagnostic and prognostic miRNA signatures in endometrial cancer

et al. 2017

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With the goal of identifying diagnostic and prognostic biomarkers in endometrial cancer, miRNA-profiling was carried out with formalin-fixed paraffin embedded (FFPE) tissue samples from 49 endometrial cancer patients. Results using an 84-cancer specific miRNA panel identified the upregulation of miR-141-3p and miR-96-5p along with a downregulation of miR-26, miR-126-3p, miR-23b, miR-195-5p, miR-374a and let-7 family of miRNAs in endometrial cancer. We validated the dysregulated expression of the identified miRNAs in a panel of endometrial cancer cell-lines. Immunohistochemical analysis of the tissue micro array derived from these patients established the functional correlation between the decreased expression of tumor suppressive miRNAs and their target oncogenes: ERBB2, EGFR, EPHA2, BAX, GNA12, GNA13, and JUN. Comparative analysis of the samples from the patients with extended progression-free survival (PFS) ( > 21 months) versus the patients with the PFS of < 21 months indicated increased expression of tumor suppressive miR-142-3p, miR-142-5p, and miR-15a-5p in samples from extended PFS patients. In addition to defining a specific set of miRNAs and their target genes as potential diagnostic biomarkers, our studies have identified tumor suppressive miR-142 cluster and miR-15a as predictors of favorable prognosis for therapy response in endometrial cancer.

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Chemotherapy-Regulated microRNA-125–HER2 Pathway as a Novel Therapeutic Target for Trastuzumab-Mediated Cellular Cytotoxicity in Small Cell Lung Cancer

Cited by 24 publications

References 34 publications

Blood and lung microRNAs as biomarkers of pulmonary tumorigenesis in cigarette smoke-exposed mice

Blood and lung microRNAs as biomarkers of pulmonary tumorigenesis in cigarette smoke-exposed mice

Oncogenic long noncoding RNA landscape in breast cancer

Identification of novel diagnostic and prognostic miRNA signatures in endometrial cancer

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