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MicroRNA-638 inhibits cell proliferation by targeting phospholipase D1 in human gastric carcinoma.

Zhang J, Bian Z, Zhou J, Song M, Liu Z, Feng Y, Zhe L, Zhang B, Yin Y, Huang Z - Protein Cell (2015)

Bottom Line: From this research, we found that miR-638 was downregulated in GC tissues compared with corresponding noncancerous tissues (NCTs), and the DNA copy number of miR-638 was lower in GC than NCTs, which may induce the corresponding downregulation of miR-638 in GC.Subsequently, we identified that PLD1 is the target gene of miR-638 in GC, and silencing PLD1 expression phenocopied the inhibitory effect of miR-638 on GC cell proliferation.In summary, we revealed that miR-638 functions as a tumor suppressor in GC through inhibiting PLD1.

View Article: PubMed Central - PubMed

Affiliation: Wuxi Oncology Institute, The Affiliated Hospital of Jiangnan University, Wuxi, 214062, China.

ABSTRACT
MicroRNAs (miRNAs) are a type of small non-coding RNAs that are often play important roles in carcinogenesis, but the carcinogenic mechanism of miRNAs is still unclear. This study will investigate the function and the mechanism of miR-638 in carcinoma (GC). The expression of miR-638 in GC and the DNA copy number of miR-638 were detected by real-time PCR. The effect of miR-638 on cell proliferation was measured by counting kit-8 assay. Different assays, including bioinformatics algorithms (TargetScan and miRanda), luciferase report assay and Western blotting, were used to identify the target gene of miR-638 in GC. The expression of miR-638 target gene in clinical CRC tissues was also validated by immunohistochemical assay. From this research, we found that miR-638 was downregulated in GC tissues compared with corresponding noncancerous tissues (NCTs), and the DNA copy number of miR-638 was lower in GC than NCTs, which may induce the corresponding downregulation of miR-638 in GC. Ectopic expression of miR-638 inhibited GC cell growth in vitro. Subsequently, we identified that PLD1 is the target gene of miR-638 in GC, and silencing PLD1 expression phenocopied the inhibitory effect of miR-638 on GC cell proliferation. Furthermore, we observed that PLD1 was overexpressed in GC tissues, and high expression of PLD1 in GC predicted poor overall survival. In summary, we revealed that miR-638 functions as a tumor suppressor in GC through inhibiting PLD1.

No MeSH data available.


Related in: MedlinePlus

Upregulation of PLD1 is inversely correlated with the miR-638 expression in GC. (A) Immunohistochemical staining of PLD1 in 120 tumor tissues and adjacent noncancerous tissues (NCTs). Brown cytoplasmic PLD1 staining was observed in GC cells but was nearly absent in normal mucosal epithelia. (B) PLD1 protein expression was frequently increased in the tumor tissues (59.3%) compared with the matched NCTs. (C) The expression levels of PLD1 were negatively correlated with the miR-638 expression levels in the GC tissues (P = 0.0062). (D) Overall survival analysis based on the expression levels of PLD1. The groups were ranked according to the PLD1 staining intensity. The patients with high PLD1 expression (scored 2 or 3) showed poor prognosis compared with low PLD1 expression (scored 0 or 1) patients (P = 0.0272)
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Fig5: Upregulation of PLD1 is inversely correlated with the miR-638 expression in GC. (A) Immunohistochemical staining of PLD1 in 120 tumor tissues and adjacent noncancerous tissues (NCTs). Brown cytoplasmic PLD1 staining was observed in GC cells but was nearly absent in normal mucosal epithelia. (B) PLD1 protein expression was frequently increased in the tumor tissues (59.3%) compared with the matched NCTs. (C) The expression levels of PLD1 were negatively correlated with the miR-638 expression levels in the GC tissues (P = 0.0062). (D) Overall survival analysis based on the expression levels of PLD1. The groups were ranked according to the PLD1 staining intensity. The patients with high PLD1 expression (scored 2 or 3) showed poor prognosis compared with low PLD1 expression (scored 0 or 1) patients (P = 0.0272)

Mentions: To further evaluate the relationship between miR-638 and PLD1 in human GC, PLD1 expression levels in GC tissues and paired NCTs were examined by IHC assay. As Fig. 5A and 5B showed, PLD1 protein expression in GC was upregulated in 71/120 cases compared with paired NCTs, and was inversely correlated with the miR-638 levels (P < 0.05, Fig. 5C), which suggested that the increased PLD1 expression in GC was caused by miR-638 under-expression. Survival analyses revealed that increased PLD1 protein levels (score 2 or 3) were associated with shorter survival time (P = 0.0272, Fig. 5D). After adjusting from tumor size, grading, and stage, multivariate analyses showed that PLD1 expression was an independent risk factor for survival (Table S1). Patients with higher PLD1 expression presented a higher risk of death (HR = 3.3049, 95% CI = 1.213–6.375, P < 0.05) (Tables S1 and S2). Taken together, these data suggest that PLD1 appears to be a new prognostic factor for GC.Figure 5


MicroRNA-638 inhibits cell proliferation by targeting phospholipase D1 in human gastric carcinoma.

Zhang J, Bian Z, Zhou J, Song M, Liu Z, Feng Y, Zhe L, Zhang B, Yin Y, Huang Z - Protein Cell (2015)

Upregulation of PLD1 is inversely correlated with the miR-638 expression in GC. (A) Immunohistochemical staining of PLD1 in 120 tumor tissues and adjacent noncancerous tissues (NCTs). Brown cytoplasmic PLD1 staining was observed in GC cells but was nearly absent in normal mucosal epithelia. (B) PLD1 protein expression was frequently increased in the tumor tissues (59.3%) compared with the matched NCTs. (C) The expression levels of PLD1 were negatively correlated with the miR-638 expression levels in the GC tissues (P = 0.0062). (D) Overall survival analysis based on the expression levels of PLD1. The groups were ranked according to the PLD1 staining intensity. The patients with high PLD1 expression (scored 2 or 3) showed poor prognosis compared with low PLD1 expression (scored 0 or 1) patients (P = 0.0272)
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Related In: Results  -  Collection

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Fig5: Upregulation of PLD1 is inversely correlated with the miR-638 expression in GC. (A) Immunohistochemical staining of PLD1 in 120 tumor tissues and adjacent noncancerous tissues (NCTs). Brown cytoplasmic PLD1 staining was observed in GC cells but was nearly absent in normal mucosal epithelia. (B) PLD1 protein expression was frequently increased in the tumor tissues (59.3%) compared with the matched NCTs. (C) The expression levels of PLD1 were negatively correlated with the miR-638 expression levels in the GC tissues (P = 0.0062). (D) Overall survival analysis based on the expression levels of PLD1. The groups were ranked according to the PLD1 staining intensity. The patients with high PLD1 expression (scored 2 or 3) showed poor prognosis compared with low PLD1 expression (scored 0 or 1) patients (P = 0.0272)
Mentions: To further evaluate the relationship between miR-638 and PLD1 in human GC, PLD1 expression levels in GC tissues and paired NCTs were examined by IHC assay. As Fig. 5A and 5B showed, PLD1 protein expression in GC was upregulated in 71/120 cases compared with paired NCTs, and was inversely correlated with the miR-638 levels (P < 0.05, Fig. 5C), which suggested that the increased PLD1 expression in GC was caused by miR-638 under-expression. Survival analyses revealed that increased PLD1 protein levels (score 2 or 3) were associated with shorter survival time (P = 0.0272, Fig. 5D). After adjusting from tumor size, grading, and stage, multivariate analyses showed that PLD1 expression was an independent risk factor for survival (Table S1). Patients with higher PLD1 expression presented a higher risk of death (HR = 3.3049, 95% CI = 1.213–6.375, P < 0.05) (Tables S1 and S2). Taken together, these data suggest that PLD1 appears to be a new prognostic factor for GC.Figure 5

Bottom Line: From this research, we found that miR-638 was downregulated in GC tissues compared with corresponding noncancerous tissues (NCTs), and the DNA copy number of miR-638 was lower in GC than NCTs, which may induce the corresponding downregulation of miR-638 in GC.Subsequently, we identified that PLD1 is the target gene of miR-638 in GC, and silencing PLD1 expression phenocopied the inhibitory effect of miR-638 on GC cell proliferation.In summary, we revealed that miR-638 functions as a tumor suppressor in GC through inhibiting PLD1.

View Article: PubMed Central - PubMed

Affiliation: Wuxi Oncology Institute, The Affiliated Hospital of Jiangnan University, Wuxi, 214062, China.

ABSTRACT
MicroRNAs (miRNAs) are a type of small non-coding RNAs that are often play important roles in carcinogenesis, but the carcinogenic mechanism of miRNAs is still unclear. This study will investigate the function and the mechanism of miR-638 in carcinoma (GC). The expression of miR-638 in GC and the DNA copy number of miR-638 were detected by real-time PCR. The effect of miR-638 on cell proliferation was measured by counting kit-8 assay. Different assays, including bioinformatics algorithms (TargetScan and miRanda), luciferase report assay and Western blotting, were used to identify the target gene of miR-638 in GC. The expression of miR-638 target gene in clinical CRC tissues was also validated by immunohistochemical assay. From this research, we found that miR-638 was downregulated in GC tissues compared with corresponding noncancerous tissues (NCTs), and the DNA copy number of miR-638 was lower in GC than NCTs, which may induce the corresponding downregulation of miR-638 in GC. Ectopic expression of miR-638 inhibited GC cell growth in vitro. Subsequently, we identified that PLD1 is the target gene of miR-638 in GC, and silencing PLD1 expression phenocopied the inhibitory effect of miR-638 on GC cell proliferation. Furthermore, we observed that PLD1 was overexpressed in GC tissues, and high expression of PLD1 in GC predicted poor overall survival. In summary, we revealed that miR-638 functions as a tumor suppressor in GC through inhibiting PLD1.

No MeSH data available.


Related in: MedlinePlus