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MicroRNA-148a is downregulated in gastric cancer, targets MMP7, and indicates tumor invasiveness and poor prognosis.

Sakamoto N, Naito Y, Oue N, Sentani K, Uraoka N, Zarni Oo H, Yanagihara K, Aoyagi K, Sasaki H, Yasui W - Cancer Sci. (2014)

Bottom Line: Downregulation of miR-148a was significantly correlated with an advanced clinical stage, lymph node metastasis, and poor clinical outcome.Custom oligonucleotide array analysis revealed that MMP7 expression was markedly downregulated in miR-148a-overexpressing GC cells; MMP7 was found to be a direct and functional target of miR-148a, participating in cell invasion.These results suggest that miR-148a contributes to the maintenance of homeostasis in normal stomach tissue and plays an important role in GC invasion by regulating MMP7 expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.

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In situ hybridization for microRNA-148a (miR-148a) and relationship between miR-148a expression and gastric caner (GC) patient prognosis. (a) MiR-148a expression in GC tissue detected by in situ hybridization. (b) Log–rank test and Kaplan–Meier plots were constructed for the miR-148a high and miR-148a low groups. Cancer-specific survival of 61 patients with GC based on the expression levels of miR-148a (cut-off line = median miR-148a expression level). (c) Cancer-specific survival of 41 patients with advanced (stage II–IV) GC based on the expression levels of miR-148a (cut-off line = median miR-148a expression level in this group).
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fig01: In situ hybridization for microRNA-148a (miR-148a) and relationship between miR-148a expression and gastric caner (GC) patient prognosis. (a) MiR-148a expression in GC tissue detected by in situ hybridization. (b) Log–rank test and Kaplan–Meier plots were constructed for the miR-148a high and miR-148a low groups. Cancer-specific survival of 61 patients with GC based on the expression levels of miR-148a (cut-off line = median miR-148a expression level). (c) Cancer-specific survival of 41 patients with advanced (stage II–IV) GC based on the expression levels of miR-148a (cut-off line = median miR-148a expression level in this group).

Mentions: To confirm the localization of miR-148a expression, in situ hybridization (ISH) was carried out using GC tissues. We could detect the miR-148a expression only in fundic glands and pyloric glands. However, neither cancer cells nor stromal tissues expressed miR-148a (Fig. 1a). Then, to further understand the relationship between miR-148a expression and clinicopathologic parameters, we examined the miR-148a expression levels in 61 formalin-fixed paraffin-embedded samples of primary GC and their corresponding non-neoplastic gastric mucosa by qRT-PCR. In this sample set, miR-148a expression levels were also significantly downregulated in GC tissue compared with corresponding non-neoplastic mucosa (Fig. S2). The expression level of miR-148a was evaluated using the tumor : normal ratio of miR-148a. The relationship between the miR-148a expression level and clinicopathologic parameters of GC is summarized in Table S1. We also evaluated the association between miR-148a expression levels and cancer-specific mortality. In all cases and in 41 advanced GC patients, the GC tissues with lower expression levels of miR-148a showed significantly worse prognosis than those with high expression (Fig. 1b,c). In order to further evaluate the association of miR-148a expression with cancer-specific mortality, we used both univariate and multivariate Cox proportional hazards analyses (Table 2). According to the univariate analysis, T grade, N grade, stage, and miR-148a expression were significantly associated with cancer-specific mortality. According to the multivariate model, expression of miR-148a was an independent prognostic classifier of cancer-specific mortality. These results indicate that loss of miR-148a may play important roles in GC progression.


MicroRNA-148a is downregulated in gastric cancer, targets MMP7, and indicates tumor invasiveness and poor prognosis.

Sakamoto N, Naito Y, Oue N, Sentani K, Uraoka N, Zarni Oo H, Yanagihara K, Aoyagi K, Sasaki H, Yasui W - Cancer Sci. (2014)

In situ hybridization for microRNA-148a (miR-148a) and relationship between miR-148a expression and gastric caner (GC) patient prognosis. (a) MiR-148a expression in GC tissue detected by in situ hybridization. (b) Log–rank test and Kaplan–Meier plots were constructed for the miR-148a high and miR-148a low groups. Cancer-specific survival of 61 patients with GC based on the expression levels of miR-148a (cut-off line = median miR-148a expression level). (c) Cancer-specific survival of 41 patients with advanced (stage II–IV) GC based on the expression levels of miR-148a (cut-off line = median miR-148a expression level in this group).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317816&req=5

fig01: In situ hybridization for microRNA-148a (miR-148a) and relationship between miR-148a expression and gastric caner (GC) patient prognosis. (a) MiR-148a expression in GC tissue detected by in situ hybridization. (b) Log–rank test and Kaplan–Meier plots were constructed for the miR-148a high and miR-148a low groups. Cancer-specific survival of 61 patients with GC based on the expression levels of miR-148a (cut-off line = median miR-148a expression level). (c) Cancer-specific survival of 41 patients with advanced (stage II–IV) GC based on the expression levels of miR-148a (cut-off line = median miR-148a expression level in this group).
Mentions: To confirm the localization of miR-148a expression, in situ hybridization (ISH) was carried out using GC tissues. We could detect the miR-148a expression only in fundic glands and pyloric glands. However, neither cancer cells nor stromal tissues expressed miR-148a (Fig. 1a). Then, to further understand the relationship between miR-148a expression and clinicopathologic parameters, we examined the miR-148a expression levels in 61 formalin-fixed paraffin-embedded samples of primary GC and their corresponding non-neoplastic gastric mucosa by qRT-PCR. In this sample set, miR-148a expression levels were also significantly downregulated in GC tissue compared with corresponding non-neoplastic mucosa (Fig. S2). The expression level of miR-148a was evaluated using the tumor : normal ratio of miR-148a. The relationship between the miR-148a expression level and clinicopathologic parameters of GC is summarized in Table S1. We also evaluated the association between miR-148a expression levels and cancer-specific mortality. In all cases and in 41 advanced GC patients, the GC tissues with lower expression levels of miR-148a showed significantly worse prognosis than those with high expression (Fig. 1b,c). In order to further evaluate the association of miR-148a expression with cancer-specific mortality, we used both univariate and multivariate Cox proportional hazards analyses (Table 2). According to the univariate analysis, T grade, N grade, stage, and miR-148a expression were significantly associated with cancer-specific mortality. According to the multivariate model, expression of miR-148a was an independent prognostic classifier of cancer-specific mortality. These results indicate that loss of miR-148a may play important roles in GC progression.

Bottom Line: Downregulation of miR-148a was significantly correlated with an advanced clinical stage, lymph node metastasis, and poor clinical outcome.Custom oligonucleotide array analysis revealed that MMP7 expression was markedly downregulated in miR-148a-overexpressing GC cells; MMP7 was found to be a direct and functional target of miR-148a, participating in cell invasion.These results suggest that miR-148a contributes to the maintenance of homeostasis in normal stomach tissue and plays an important role in GC invasion by regulating MMP7 expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.

Show MeSH
Related in: MedlinePlus