• Asian Pacific Journal of Cancer Prevention
• /
• 제15권9호
• /
• pp.4033-4037
• /
• 2014

Emerging evidence has shown associations of microRNA-205 (miR-205) with crucial cell processes such as the epithelial-mesenchymal transition (EMT) and aberrant expression with tumorigenesis in many types of human malignancy. This prospective study characterized the contribution of miR-205 to the colorectal cancer (CRC) tumorigenesis. The real-time reverse transcription-polymerase chain reaction was used to examine miR-205 levels prospectively in 36 pairs of samples of CRC tissue and adjacent noncancerous tissue (>2 cm from cancer tissue). In addition, the relationship between miR-205 levels and clinicopathological features was explored. The capability of miR-205 to function as a tumor marker was also examined. miR-205 expression levels did not show significant changes overall. However, miR-205 was significantly downregulated in a group of CRC samples compared with matched noncancerous tissue samples. Moreover, decreased miR-205 correlated significantly with lymphatic metastasis. A receiver operating characteristic (ROC) curve also showed an optimum cut off point of $1.4{\times}10^{-3}$ to distinguish lymphatic metastatic CRCs from non-metastatic CRCs. Interestingly we found lymphatic metastasis in almost 80% of the depressed samples. This study suggested that miR-205 could be reduced in the majority of metastatic CRCs and the risk of CRC metastasis may be predicted by monitoring miR-205 in patient samples collected at the time of the initial diagnosis. Therefore, targeting miR-205 and its potential environmental activators might be a promising therapeutic option to prevent malignant progression toward metastasis.

• Molecules and Cells
• /
• 제41권6호
• /
• pp.532-544
• /
• 2018

Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. In order to investigate a new treatment fot GIST, we hypothesized the effect of miR-374b targeting PTEN gene-mediated PI3K/Akt signal transduction pathway on proliferation and apoptosis of human gastrointestinal stromal tumor (GIST) cells. We obtained GIST tissues and adjacent normal tissues from 143 patients with GIST to measure the levels of miR-374b, PTEN, PI3K, Akt, caspase9, Bax, MMP2, MMP9, ki67, PCNA, P53 and cyclinD1. Finally, cell viability, cell cycle and apoptosis were detected. According to the KFGG analysis of DEGs, PTEN was involved in a variety of signaling pathways and miRs were associated with cancer development. The results showed that MiR-374b was highly expressed, while PTEN was downregulated in the GIST tissues. The levels of miR-374b, PI3K, AKT and PTEN were related to tumor diameter and pathological stage. Additionally, miR-374b increased the mRNA and protein levels of PI3K, Akt, MMP2, MMP9, P53 and cyclinD1, suggesting that miR-374b activates PI3K/Akt signaling pathway in GIST-T1 cells. Moreover, MiR374b promoted cell viability, migration, invasion, and cell cycle entry, and inhibited apoptosis in GIST cells. Taken together, the results indicated that miR-374b promotes viability and inhibits apoptosis of human GIST cells by targeting PTEN gene through the PI3K/Akt signaling pathway. Thus, this study provides a new potential target for GIST treatment.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권4호
• /
• pp.1511-1515
• /
• 2014

Background and Aims: To explore the molecular mechanisms of miR-886-5p in breast cancer., we examined roles in inhibiting growth and migration of MCF-7 cells. Methods: MiR-886-5p mimics and inhibitors were used to express or inhibit MiR-886-5p, respectively, and MTT and clone formation assays were used to determine the survival and proliferation. Hoechst 33342/ PI double staining was applied to detect apoptosis. The expression of caspase-3, caspase-8, caspase-9, MT1-MMP, VEGF-C and VEGF-D was detected by Western blotting, and the levels of MMP2 and MMP9 secreted from MCF-7 cells were assessed by ELISA. MCF-7 cell migration was determined by wound healing and Transwell assays. Results: We found that the growth of MCF-7 cells was inhibited upon decreasing miR-886-5p levels. Inhibiting miR-866-5p also significantly induced apoptosis and decreased the migratory capacity of these cells. The expression of VEGF-C, VEGF-D, MT1-MMP, MMP2, and MMP9 was also found to be decreased as compared to controls. Conclusions: Our data show that downregulation of miR-886-5p expression in MCF-7 cells could significantly inhibit cell growth and migration. This might imply that inhibiting miR-886-5p could be a therapeutic strategy in breast cancer.

• Nutrition Research and Practice
• /
• 제14권4호
• /
• pp.412-422
• /
• 2020

BACKGROUND/OBJECTIVES: This study investigates correlations between circulating microRNAs (miRNAs) and obesity-related parameters among young women (aged 20-30 years old) in Korea. SUBJECTS/METHODS: We analyzed TaqMan low density arrays (TLDAs) of circulating miRNAs in 9 lean (body mass index [BMI] < 25 kg/㎡) and 15 obese (BMI > 25 kg/㎡) women. We also performed gene ontology (GO) analyses of the biological functions of predicted miRNA target genes, and clustered the results using the database for annotation, visualization and integrated discovery. RESULTS: The TLDA cards contain 754 human miRNAs; of these, the levels of 8 circulating miRNAs significantly declined (> 2-fold) in obese subjects compared with those in lean subjects, including miR-1227, miR-144-5p, miR-192, miR-320, miR-320b, miR-484, miR-324-3p, and miR-378. Among them, miR-484 and miR-378 displayed the most significant inverse correlations with BMI (miR-484, r = -0.5484, P = 0.0056; miR-378, r = -0.5538, P = 0.0050) and visceral fat content (miR-484, r = -0.6141, P = 0.0014; miR-378, r = -0.6090, P = 0.0017). GO analysis indicated that genes targeted by miR-484 and miR-378 had major roles in carbohydrate and lipid metabolism. CONCLUSION: Our result showed the differentially expressed circulating miRNAs in obese subjects compared to lean subjects. Although the mechanistic study to reveal the causal role of miRNAs remains, these miRNAs may be novel biomarkers for obesity.

• Journal of Microbiology and Biotechnology
• /
• 제31권7호
• /
• pp.921-932
• /
• 2021

LINC01272 is a long non-coding RNA (lncRNA) that has been considered as a biomarker for many diseases including lung squamous cell carcinoma. Here, we investigated the function and mechanism of LINC01272 on lung cancer (LC). The differential expression of LINC01272 in LC and normal samples was analyzed by GEPIA based on the data from TCGA-LUAD database, as survival prognosis was analyzed through Kaplan-Meier Plotter. LINC01272 overexpression plasmid and miR-7-5p mimic were transfected into A549 and PC-9 cells. LINC01272, miR-7-5p and cardiolipin synthase 1 (CRLS1) mRNA expression was measured by quantitative reverse transcription-polymerase chain reaction. Cell viability was detected through MTT assay. Cell multiplication was evaluated by cell formation assay. Cell apoptosis was assessed through flow cytometry assay. Through bioinformatics, the target miRNA of LINC01272 and downstream genes of miR-7-5p were predicted. The targeting relationship was tested by dual luciferase reporter analysis. CRLS1, B-cell lymphoma-2 (Bcl-2), BCL2-associated X (Bax) and cleaved caspase-3 protein levels were detected through western blot. LINC01272 was downregulated in LC and low LINC01272 expression had poor prognosis. In A549 and PC-9 cells, LINC01272 inhibited cell viability and multiplication and induced apoptosis. LINC01272 negatively regulated miR-7-5p and CRLS1 was a target of miR-7-5p. MiR-7-5p reversed the effect of LINC01272 on viability, multiplication, apoptosis and expression of miR-7-5p and CRLS1 as well as apoptosis-related factors (Bcl-2, Bax and cleaved caspase-3). LINC01272 suppressed cell multiplication and induced apoptosis via regulating the miR-7-5p/CRLS1 axis in LC.

• BMB Reports
• /
• 제45권11호
• /
• pp.641-646
• /
• 2012

It has been reported that ubiquitin-conjugating enzyme 9 (Ubc9), the unique enzyme2 in the sumoylation pathway, is up-regulated in many cancers. However, the expression and regulation of UBC9 in glioma remains unknown. In this study, we found that Ubc9 was up-regulated in glioma tissues and cell lines compared to a normal control. UBC9 knockdown by small interfering RNA (siRNA) affected cell proliferation and apoptosis in T98G cells. Further experiments revealed that microRNA (miR)-214 directly targeted the 3' untranslated region (UTR) of UBC9 and that there was an inverse relationship between the expression levels of miR-214 and UBC9 protein in glioma tissues and cells. miR-214 overexpression suppressed the endogenous UBC9 protein and affected T98G cell proliferation. These findings suggest that miR-214 reduction facilitates UBC9 expression and is involved in the regulation of glioma cell proliferation.

• BMB Reports
• /
• 제52권9호
• /
• pp.572-576
• /
• 2019

Bisphosphonates are the mainstay of therapy worldwide for osteoporosis. However, bisphosphonates also have limitations. The objective of this study was to determine the role of miR-101-3p/Rap1b signal pathway in osteoclast differentiation after treatment with bisphosphonates. Our results revealed that miR-101-3p was an important regulator in bisphosphonates treated-osteoclasts. When miR-101-3p was down-regulated in bone marrow-derived macrophage-like cells (BMMs), the development of mature osteoclasts was promoted, and vice versa. However, alendronate decreased multinucleated cell number regardless of whether miR-101-3p was knocked down or over-expressed. TRAP activity assay confirmed the above results. Luciferase assay indicated that miR-101-3p was a negative regulator of Rap1b. Western blot analysis revealed that protein expression level of Rap1b in BMMs transfected with OV-miR-101-3p was lower than that in BMMs transfected with an empty vector. Rap1b overexpression increased TRAP-positive multinucleated cells, while Rap1b inhibition decreased the cell numbers. In vivo data showed that miR-101-3p inhibited osteoclast differentiation in ovariectomized mice while overexpressed of Rap1b blocked the differentiation. Taken together, our data demonstrate that miR-101-3p/Rap1b signal pathway plays a key role in osteoclast differentiation after treatment with bisphosphonates.

• BMB Reports
• /
• 제47권9호
• /
• pp.500-505
• /
• 2014

Colorectal cancer has become the third most common cancer and leads to high mortality worldwide. Although colorectal cancer has been studied widely, the underlying molecular mechanism remains unclear. PER3 is related to tumor differentiation and the progression of colorectal cancer. High expression of miR-103 is associated with poor prognosis in patients with colorectal cancer. However, the relationship between miR-103 and PER3 in CRC cells remains unclear. In this study, we found that PER3 was downregulated in CRC tissues and CRC cell lines, whereas miR-103 was upregulated in CRC cell lines. We also found that PER3 promoted CRC cells apoptosis. These results indicate that PER3 plays a suppressive role in CRC cells. Moreover, we found that PER3 was targeted, at least partially, by miR-103. Taken together, we provide evidence to characterize the role of PER3 in CRC, which may be a new therapeutic target for CRC.

• Asian-Australasian Journal of Animal Sciences
• /
• 제32권9호
• /
• pp.1469-1474
• /
• 2019

Objective: Physical activity restriction in sows may lead to behavioral abnormalities and affective disorders. However, the psychophysiological state of these sows is still unclear. As miRNAs can be used as effective markers of psychopathy, the present study aimed to assess the difference in microRNA expression between the long-term activity restricted sows and activity free sows, thus contributing to the understanding of abnormal sow behavior. Methods: Four dry sows (sixth parity, Large${\times}$White genetic line) were selected from activity restricted crates (RC) or activity free pens (FP) separately. microRNAs in the ventromedial prefrontal cortex (vMPFC) and serum were examined using real-time polymerase chain reaction, and the correlation between the miRNAs expressed in the vMPFC and serum was evaluated. Results: miR-134 (1.11 vs 0.84) and miR-1202 (1.09 vs 0.85) levels were higher in the vMPFC of the RC sows than in the FP sows (p<0.01). Furthermore, miR-132 (1.27 vs 1.08) and miR-335 (1.03 vs 0.84) levels were also higher in the RC sows than in FP sows (p<0.05); however, miR-135a, miR-135b, miR-16, and miR-124 levels were not different (p>0.05). The relative expression of serum miR-1202 was higher in the RC sows than in the FP sows (1.04 vs 0.54) (p<0.05), and there was a strong correlation (R = 0.757, p<0.05) between vMPFC and Serum levels of miR-1202. However, no significant difference was observed in miR-16 levels in the serum of the RC sows and FP sows (p>0.05). Conclusion: This pilot study demonstrates that long-term activity restriction in sows likely results in autism or other complex psychopathies with depression-like behaviors. These observations may provide new insights for future studies on abnormal behavior in sows and contribute to research on human psychopathy.

• Molecules and Cells
• /
• 제37권9호
• /
• pp.664-671
• /
• 2014

MiR-217 can function as an oncogene or a tumour suppressor gene depending on cell type. However, the function of miR-217 in lung cancer remains unclear to date. This study aims to evaluate the function of miR-217 in lung cancer and investigate its effect on the sensitivity of lung cancer cells to cisplatin. The expression of miR-217 was detected in 100 patients by real-time PCR. The effects of miR-217 overexpression on the proliferation, apoptosis, migration and invasion of SPC-A-1 and A549 cells were investigated. The target gene of miR-217 was predicted by Targetscan online software, screened by dual luciferase reporter gene assay and demonstrated by Western blot. Finally, the effects of miR-217 up-regulation on the sensitivity of A549 cells to cisplatin were determined. The expression of miR-217 was significantly lower in lung cancer tissues than in noncancerous tissues (p < 0.001). The overexpression of miR-217 significantly inhibited the proliferation, migration and invasion as well as promoted the apoptosis of lung cancer cells by targeting KRAS. The up-regulation of miR-217 enhanced the sensitivity of SPC-A-1 and A549 cells to cisplatin. In conclusion, miR-217 suppresses tumour development in lung cancer by targeting KRAS and enhances cell sensitivity to cisplatin. Our results encourage researchers to use cisplatin in combination with miR-217 to treat lung cancer. This regime might lead to low-dose cisplatin application and cisplatin side-effect reduction.