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Dysregulation of microRNA biosynthesis enzyme Dicer plays an important role in gastric cancer progression.

ABSTRACT: BACKGROUND AND AIM: Dicer is one of the most important components in microRNA biogenesis. Although studies have revealed the aberrantly expression of Dicer in types of cancer, the results were greatly controversial. Here we aimed to study the expression of Dicer in gastric cancer (GC) and further explored the possible roles of Dicer in cancer progression. METHODS: The alteration of Dicer-expression in GC and its clinical significance was retrospectively studied with immunohistochemical analyses on 377 cases of cancer tissues using tissue microarray (TMA). Dicer mRNA and protein levels were also examined in 8 paired of GC tissues and non-neoplastic surrounding gastric epithelium with real time RT-PCR and western blot. RESULTS: We found that Dicer was reduced in GC tissues in both mRNA and protein levels. Moreover, down-regulation of Dicer was correlated highly with tumor differentiation (P<0.05) and lymph node invasion (P<0.05) in GC tissues, which suggested an essential role of Dicer in cancer invasion. CONCLUSIONS: Considering that Dicer might be closely related to progression of GC, we proposed that Dicer might offer a promising target for prevention of metastatic progression in GC.

SUBMITTER: Zhang J

PROVIDER: S-EPMC4014251 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Dysregulation of microRNA biosynthesis enzyme Dicer plays an important role in gastric cancer progression.

Zhang Jin J Zhang Xin-Hua XH Wang Cai-Xia CX Liu Biao B Fan Xiang-Shan XS Wen Juan-Juan JJ Shi Qun-Li QL Zhou Xiao-Jun XJ

International journal of clinical and experimental pathology 20140315 4

<h4>Background and aim</h4>Dicer is one of the most important components in microRNA biogenesis. Although studies have revealed the aberrantly expression of Dicer in types of cancer, the results were greatly controversial. Here we aimed to study the expression of Dicer in gastric cancer (GC) and further explored the possible roles of Dicer in cancer progression.<h4>Methods</h4>The alteration of Dicer-expression in GC and its clinical significance was retrospectively studied with immunohistochemi ...[more]

PMID: 24817967

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Project description:BackgroundPolypyrimidine tract binding protein 1 (PTBP1) has been found to play an important role in the occurrence and development of various tumors. At present, the role of PTBP1 in gastric cancer (GC) is still unknown and worthy of further investigation.MethodsWe used bioinformatics to analyze the expression of PTBP1 in patients with GC. Cell proliferation related experiments were used to detect cell proliferation after PTBP1 knockdown. Skeleton staining, scanning electron microscopy and transmission electron microscopy were used to observe the changes of actin skeleton. Proliferation and actin skeleton remodeling signaling pathways were detected by Western Blots. The relationship between PTBP1 and proliferation of gastric cancer cells was further detected by subcutaneous tumor transplantation. Finally, tissue microarray data from clinical samples were used to further explore the expression of PTBP1 in patients with gastric cancer and its correlation with prognosis.ResultsThrough bioinformatics studies, we found that PTBP1 was highly expressed in GC patients and correlated with poor prognosis. Cell proliferation and cycle analysis showed that PTBP1 down-regulation could significantly inhibit cell proliferation. The results of cell proliferation detection related experiments showed that PTBP1 down-regulation could inhibit the division and proliferation of GC cells. Furthermore, changes in the morphology of the actin skeleton of cells showed that PTBP1 down-regulation inhibited actin skeletal remodeling in GC cells. Western Blots showed that PTBP1 could regulate proliferation and actin skeleton remodeling signaling pathways. In addition, we constructed PTBP1 Cas9-KO mouse model and performed xenograft assays to further confirm that down-regulation of PTBP1 could inhibit the proliferation of GC cells. Finally, tissue microarray was used to further verify the close correlation between PTBP1 and poor prognosis in patients with GC.ConclusionsOur study demonstrates for the first time that PTBP1 may affect the proliferation of GC cells by regulating actin skeleton remodeling. In addition, PTBP1 is closely related to actin skeleton remodeling and proliferation signaling pathways. We suppose that PTBP1 might be a potential target for the treatment of GC.

Dataset Information

Dysregulation of microRNA biosynthesis enzyme Dicer plays an important role in gastric cancer progression.

Publications

Dysregulation of microRNA biosynthesis enzyme Dicer plays an important role in gastric cancer progression.

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