Recent studies have emphasized the important role of microRNA (miRNA) clusters and common target genes in disease progression. Despite the known involvement of the miR‐192/215 family in many human diseases, its biological role in Hirschsprung disease (HSCR) remains undefined. In this study, we explored the role of the miR‐192/215 family in the pathogenesis of HSCR. Quantitative real‐time PCR and western blotting measured relative expression levels of miRNAs, mRNAs, and proteins in 80 HSCR patients and 77 normal colon tissues. Targets were evaluated by dual‐luciferase reporter assays, and the functional effects of miR‐192/215 on human 293T and SH‐SY5Y cells were detected by the Transwell assay, CCK8 assay and flow cytometry. MiR‐192/215 was significantly down‐regulated in HSCR tissue samples, and their knockdown inhibited cell migration and proliferation in the human 293T and SH‐SY5Y cell lines. Nidogen 1 (NID1) was confirmed as a common target gene of miR‐192/215 by dual‐luciferase reporter gene assay and its expression was inversely correlated with that of miR‐192/215 in tissue samples and cell lines. Silencing of NID1 could rescue the extent of the suppressing effects by miR‐192/215 inhibitor. The down‐regulation of miR‐192/215 may contribute to HSCR development by targeting NID1.
Accurate assessment of human epidermal growth factor receptor (HER) 2 is essential for efficient selection of patients who
may benefit from therapies targeting this surface receptor (e.g., trastuzumab). Intratumoral heterogeneity of HER2 expression
may potentially contribute to inaccurate assessment of HER2 status. To clarify intratumoral heterogeneity of HER2 expression
and its potential clinical impact on assessment of HER2 status, we analyzed 148 endoscopic biopsy specimens and 117 excisional
tumor specimens collected from 148 patients with primary gastric cancer. Specifically, we assessed HER2 protein overexpression
and gene amplification using, respectively, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). There
were 28 IHC-positive cases and 25 FISH-positive cases among these 148 patients. Heterogeneous HER2 protein expression was
demonstrated in 23 of 29 (79.3%) IHC-positive cases, while gene expression heterogeneity was found in 11 of 25 (44.0%) FISH-positive
cases. Intratumoral heterogeneity was the main reason of discordant results between IHC and FISH or between endoscopic biopsy
and excisional tumor specimens. The clinical significance and impact of intratumoral HER2 expression heterogeneity on treatment
outcome in gastric cancer require further studies. 相似文献
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