Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0005684 (bladder cancer)
 16,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The LASS2 gene has been identified as a new tumor metastasis suppressor gene and has been seen to correlate with the degree of invasion and recurrence in carcinomas of prostate, breast, liver, ovarian, and pancreas. However, expression and prognostic significance of LASS2 in human bladder carcinoma are largely unknown. In this study, the protein expression of LASS2 in 80 patients with different stages was detected by immunohistochemical staining. The prognostic value of LASS2 in bladder cancers can also be assessed by a long-term follow-up investigation. The mRNA expression level of the LASS2 gene was examined using real-time quantitative PCR (qPCR) in human bladder carcinoma and paired non-tumor bladder tissues, which were obtained from 30 patients who underwent total cystectomy. We found that patients with LASS2-negative bladder cancer were linked to poor clinical prognosis. The expression of LASS2 mRNA was significantly correlated with clinical stage (P < 0.001), depth of tumor invasion (P < 0.001), and recurrence (P < 0.001). Thus, LASS2 expression may be correlated with the development and progression of human bladder carcinoma and may be a prognostic indicator for this carcinoma.
 ...
PMID:Expression and prognostic significance of a new tumor metastasis suppressor gene LASS2 in human bladder carcinoma. 2175 71

Bladder cancer is one of the most common cancers and, together with prostate carcinoma, accounts for the majority of the malignancies of the genitourinary tract. Since prognosis ameliorates with early detection, it will be beneficial to have a repertoire of diagnostic markers that could complement the current diagnosis protocols. Recently, cell-secreted extracellular vesicles have received great interest as a source of low invasive disease biomarkers because they are found in many body fluids, including urine. The current work describes a pilot study to generate an array-based catalogue of mRNA associated to urinary vesicles, and also a comparison with samples obtained from bladder cancer patients. After an analysis of presence/absence of transcripts in bladder cancer EVs, a list of genes was selected for further validation using PCR technique. We found four genes differentially expressed in cancer samples. LASS2 and GALNT1 were present in cancer patients, while ARHGEF39 and FOXO3 were found only in non-cancer urinary vesicles. Previous studies have pointed to the involvement of those genes in tumour progression and metastasis.
...
PMID:A Pilot Study on the Potential of RNA-Associated to Urinary Vesicles as a Suitable Non-Invasive Source for Diagnostic Purposes in Bladder Cancer. 2445 10

MicroRNA-9 upregulation was reported in several tumors. However, its function and mechanism in human bladder cancer remains obscure. The present study aims to identify the expression pattern, biological roles and potential mechanism of miR-9 in human bladder cancers. We found that expression level of miR-9 in bladder cancer tissues was higher than normal tissues. miR-9 mimic transfection was performed in T24 and 5637 cells with low miR-9 expression, and miR-9 inhibitor was employed in BIU-87 cell line with high endogenous expression. miR-9 increased cell proliferation, cell cycle progression, invasion and chemoresistance, with upregulation of cyclin D1, MMP9, Bcl-2, and survivin and downregulation of E-cadherin. Using luciferase reporter assay, we confirmed that LASS2 was a direct target of miR-9 in bladder cancer cells. Transfection of miR-9 mimic downregulated LASS2 expression. LASS2 transfection downregulated Bcl-2 and survivin expression, which were induced by miR-9 mimic in both cell lines. In conclusion, these results indicate that miR-9 upregulation might be associated with malignant phenotype of bladder cancer. miR-9 promotes chemoresistance of bladder cancer cells by target LASS2.
 ...
PMID:miR-9 promotes cell proliferation and inhibits apoptosis by targeting LASS2 in bladder cancer. 2615 Mar 38

The aberrant expression of miRNA has an important function in bladder cancer (BC). Previous studies indicate that LASS2 is involved in the development of sensitivity to chemotherapy in cancer cells. In the present study, the miRNAs related to LASS2 were selected by using miRNA profiling to distinguish chemo-resistant and chemo-sensitive tumor specimens from patients. Higher levels of miR-93 were observed in the cisplatin-resistant BC cell line RT4, compared to the cell line T24. The role of miR-93 in chemo-sensitivity was demonstrated both in cell culture and mouse tumor xenograft models. We found that inhibiting miR-93 promoted cisplatin-induced apoptosis due to the accumulation of DNA damage. A reporter gene assay was performed, and the results showed miR-93 was not a target of the 3' untranslated region of LASS2, but had an altered protein expression level. Inhibitors of miR-93 could also enhance the chemo-sensitivity of tumor cells transfected with si-LASS2, but the effect was very slight. These findings suggest that miR-93 plays an important role in the chemo-sensitivity of BC, and may be involved in regulating the LASS2 gene.
...
PMID:Repression of the miR-93-enhanced sensitivity of bladder carcinoma to chemotherapy involves the regulation of LASS2. 2709 14

Mitochondria coordinated a lot of vital cellular processes of energy production and distribution. Change of mitochondrial functions has been implicated in cancer progression. The present study aims to investigate the involvement of mitochondria dynamics in LASS2 induced invasion and chemoresistance of bladder cancer cells. J82 and BIU87 cell lines were used for LASS2 plasmid transfection while siRNA knockdown was carried out in 5637 cell line. Matrigel invasion assay and Annexin V/PI staining demonstrated that LASS2 negatively regulated cancer cell invasion and chemoresistance. JC-1 staining suggested that LASS2 overexpression downregulated mitochondrial membrane potential. Mitotracker staining showed that LASS2 induced mitochondrial fusion and inhibited mitochondrial fission. In addition, LASS2 overexpression downregulated expression of mitochondrial fission protein p-Drp1 Drp1 and Fis1. While depletion of LASS2 exhibited the opposite effects. Drp1 inhibitor Mdivi abolished invasion and chemoresistance induced by LASS2 siRNA. Furthermore, we found that LASS2 overexpression could inhibit phosphorylation of ERK, which act upstream of Drp1. ERK inhibitor PD98059 suppressed Drp1 phosphorylation and abrogated the effects of LASS2 depletion. In conclusion, the present study demonstrated that LASS2 inhibits bladder cancer invasion and chemoresistance through regulation of ERK-Drp1 induced mitochondrial dynamics.
 ...
PMID:LASS2 regulates invasion and chemoresistance via ERK/Drp1 modulated mitochondrial dynamics in bladder cancer cells. 2958 81

Transcription factor proto-oncogene TWIST1 and tumor metastasis suppressor gene LASS2 have been reported to be involved in various carcinomas but their expression profiles and prognostic significances in bladder cancer are largely unknown. We aimed to determine these genes' expression levels both at mRNA and protein level in bladder cancer. mRNA expression levels of TWIST1 and LASS2 genes were examined using real-time quantitative PCR (qPCR) in human bladder tumors and paired normal adjacent tissues obtained from 44 patients. Protein expression profiles of both genes were detected by immunohistochemical staining in formalin-fixed and paraffin-embedded tissues from the same patients. The expression profiles of TWIST1 mRNA in bladder tumors were significantly lower than the normal adjacent tissues and linked to both the stage and the grade. The expression profiles of LASS2 mRNA in bladder tumors were also significantly lower than the normal adjacent tissues reflecting the potential tumor suppressor profile of the gene, independently from stage or grade. By immunohistochemistry, TWIST1 and LASS2 positive expression rates were found as 14.3% (6/42) and 38.1% (16/42), respectively. As potential molecular markers for bladder carcinoma, both TWIST1 and LASS2 transcripts seem to play role during the tumorigenesis and development of bladder cancer. Lack of a functional link and/or weak inverse link between TWIST1 and LASS2 transcripts and immunohistochemical findings may reflect the potential associations of transcription regulation mechanisms and merit further investigations. To the best of our knowledge, this is the first report investigating the combined expression profile of TWIST1 and LASS2 in bladder cancer both at mRNA and protein level.
 ...
PMID:Expression profiles of proto-oncogene TWIST1 and tumor metastasis suppressor gene LASS2 in bladder cancer. 3021 91

MicroRNA-98(miR-98) has been shown to be critical for tumorigenesis, however its involvement in bladder cancer are unclear. The present study aims to investigate the expression, biological roles and potential mechanisms of miR-98 in human bladder cancer. We found that miR-98 was upregulated in bladder urothelial carcinoma tissues compared with adjacent normal tissues. In addition, miR-98 expression was higher in bladder cancer cell lines than in uroepithelial cell line SV-HUC-1. Functional studies revealed that miR-98 mimic promoted proliferation of T24 cells while miR-98 inhibitor inhibited proliferation of BIU-87 cells. Moreover, miR-98 mimic increased cisplatin/doxorubicin resistance and inhibited apoptosis in T24 cells, while miR-98 inhibitor decreased chemoresistance and facilitated apoptosis in BIU-87 cells. Further experiments using MitoTracker and JC-1 staining showed that miR-98 could regulate mitochondrial fission/fusion balance and mitochondrial membrane potential. Western blot showed that miR-98 upregulated cyclin D1, p-Drp1 and Drp1. Using luciferase reporter assay, we demonstrated that LASS2 acted as a direct target of miR-98. LASS2 overexpression induced mitochondrial fusion and downregulated mitochondrial potential, with decreased p-Drp1 status. Additionally, LASS2 siRNA abrogated the effects of miR-98 mimic on Drp1phosphorylation and chemoresistance. We also found a negative correlation between LASS2 and miR-98 in bladder cancer tissues. In conclusion, our study demonstrates that miR-98 targets LASS2 and regulates bladder cancer chemoresistance through modulation of mitochondrial function.
 ...
PMID:MicroRNA-98 promotes drug resistance and regulates mitochondrial dynamics by targeting LASS2 in bladder cancer cells. 3046 87

As a tumor metastasis suppressor gene, LASS2 has been found to be negatively associated with the stage of bladder cancer and overall survival of patients. However, the mechanisms regulating LASS2 in bladder cancer remain poorly understood. Here, we aim to identify a miRNA that targets LASS2 from bladder cancer-associated miRNAs and to reveal its potential functions in bladder cancer cells. Through miRNA microarray and bioinformatics analyses, we identified miR-3622a as a negative regulator of LASS2. The expression levels of miR-3622a in bladder cancer tissues were negatively correlated with the overall survival of patients. Overexpression of miR-3622a significantly increased the proliferation and invasion abilities of bladder cancer cells. In conclusion, our results indicate that miR-3622a promotes the proliferation and invasion of bladder cancer cells by downregulating LASS2.
 ...
PMID:miR-3622a promotes proliferation and invasion of bladder cancer cells by downregulating LASS2. 3089 13

The aim of the present study was to explore the correlations between single nucleotide polymorphisms in LASS2 gene 3'-untranslated regions and bladder cancer risk in Chinese population. We first performed PCR and sequence for LASS2-3'-UTR in 105 bladder cancer patients and 100 control subjects. Next, multivariate logistic regression analysis was used to determine the relationship between single nucleotide polymorphisms frequency and susceptibility of bladder cancer, and clinical features in 105 cases. In addition, survival curves and Cox Regression analysis were used to investigate the effect of single nucleotide polymorphisms on clinical outcome in 58 cases. Finally, quantitative reverse-transcription PCR and immunohistochemical were performed to explore the influence of single nucleotide polymorphisms on LASS2 expression. We found that a single nucleotide polymorphism (rs8444 C>T) located in the 3'-UTR of LASS2 was significantly associated with the risk of bladder cancer. We also showed the frequency of rs8444 T genotype was higher in bladder cancer group and correlated with the risk of clinical prognosis. Yet, there were no significant correlations between T/C allele frequencies and the distributions of rs8444 genotype and tumor-node-metastasis stage, histological grade and distant metastasis in bladder cancer. Furthermore, we demonstrated that rs8444 C>T could affect LASS2 expression by single nucleotide polymorphism-related mRNA stability. Our results showed that LASS2-3'-UTR rs8444 C>T polymorphism was significantly associated with the individual risk and the poor overall survival of bladder cancer, suggesting that rs8444 TT genotype maybe act as an independent risk factor of susceptibility and clinical prognosis for bladder cancer in Chinese population.
 ...
PMID:Association of rs8444 polymorphism in the LASS2 3'-UTR and bladder cancer risk in Chinese population. 3157 63