Overexpression of SNHG12 regulates the viability and invasion of renal cell carcinoma cells through modulation of HIF1α.

BACKGROUND: Cumulative evidences demonstrated the aberrant overexpression of Small Nucleolar RNA Host Gene 12 (SNHG12) in diverse human cancer. However, the expression status and involvement of SNHG12 in renal cell carcinoma is still elusive. METHODS: The expression of SNHG12 was determined by q-PCR. The transcriptional regulation was interrogated by luciferase reporter assay. Cell viability was measured with CCK-8 kit. The anchorage-independent was evaluated by soft agar assay. Cell apoptosis was analyzed by Annexin V/7-AAD double staining. The migration and invasion were determined by trans-well assay and wound scratch closure. The in vivo tumor growth was monitored in xenograft mice model. Protein expression was quantified by immunoblotting. RESULTS: SNHG12 was aberrantly up-regulated in renal carcinoma both in vivo and in vitro. High expression of SNHG12 associated with poor prognosis. Deficiency of SNHG12 significantly suppressed cell viability, anchorage-independent growth and induced apoptosis. In addition, SNHG12 silencing inhibited migrative and invasive in vitro and xenograft tumor growth in vivo. Mechanistically, SNHG12 modulated HIF1α expression via competing with miR-199a-5p, which consequently contributed to its oncogenic potential. MiR-199a-5p inhibition severely compromised SNHG12 silencing-elicited tumor repressive effects. CONCLUSION: Our data uncovered a crucial role of SNHG12-miR-199a-5p-HIF1α axis in human renal cancer.

miR-19 promotes the proliferation of clear cell renal cell carcinoma by targeting the FRK-PTEN axis.

BACKGROUND: The non-receptor tyrosine kinase Fyn-related kinase (FRK) has been reported to affect cell proliferation in several cancer types. However, its effect on the proliferation of clear cell renal cell carcinoma (ccRCC) remains largely unknown. PURPOSE: The objective of this study was to investigate the expression pattern and function of FRK in ccRCC. We further determined how FRK interacted with other molecules to regulate ccRCC proliferation. PATIENTS AND METHODS: The expression of FRK in ccRCC samples and paired normal renal tissues from 30 patients were analyzed by immunoblotting, immunohistochemistry and quantitative PCR. Then the role of FRK in ccRCC proliferation was analyzed by Cell Counting Kit-8, colony formation assay and EdU incorporation assay. In addition, the miRNA targeting FRK was predicted through a bioinformatic approach and validated by quantitative PCR, immunoblotting and luciferase reporter assay. Finally, the underlying mechanism of FRK regulation of ccRCC proliferation was also determined. RESULTS: Low expression of FRK was detected in ccRCC samples and predicted poor survival for ccRCC patients. FRK inhibited the proliferation of ccRCC cells via phosphorylating downstream PTEN. miR-19 was identified as a novel suppressor of FRK in renal cancer cells and it promoted the proliferation of ccRCC by inhibiting the FRK-PTEN axis. CONCLUSION: Our results unravel a new regulatory mechanism involved in ccRCC proliferation and may be useful in the identification of therapeutic targets for ccRCC.

TRPM7 is overexpressed in bladder cancer and promotes proliferation, migration, invasion and tumor growth.

Recent findings suggest that the melastatin transient receptor potential channel 7 (TRPM7) is overexpressed in many types of cancers and is involved in tumorigenesis. However, its expression pattern and the potential role in bladder cancer remain unclear. The aim of the present study was to investigate the expression status of TRPM7 and its relationship with the development of bladder cancer. In the present study, we observed that the expression of TRPM7 was significantly elevated in bladder cancer tissues compared with that noted in the adjacent non-tumor tissues. Furthermore, increased TRPM7 expression was significantly associated with recurrence, metastasis and prognosis. In addition, after knockdown of the expression of TRPM7 by siRNA, the proliferation and the motility of T24 and 5637 cells were obviously inhibited, and downregulation of TRPM7 was found to play an important role in bladder cancer cell apoptosis. In conclusion, our findings suggest that TRPM7 plays an important role in bladder cancer, and TRPM7 may serve as a potentially unfavorable factor and novel target for human bladder cancer.

Systematic analysis on the GSTM1 null phenotype and prostate cancer risk in Chinese people.

OBJECTIVE: Glutathione S-transferase M 1 (GSTM1) is implicated as a risk factor for prostate cancer. However, this issue is not clear in Chinese population. This systemic analysis was conducted to evaluate the effect of GSTM1 null genotypes on prostate cancer risk in Chinese. METHODS: Published studies investigating the associations between GSTM1 null genotypes and the risk of prostate cancer in China were identified by using a predefined search strategy. Main statisticals were pooled and estimated according to the primarily reported data. RESULTS: The prevalence of the GSTM1 null genotype was higher in prostate cancer patients than in controls, with significance. CONCLUSION: The GSTM1 null genotypes is associated with increased risk of prostate cancer in Chinese.

Ursolic acid overcomes Bcl-2-mediated resistance to apoptosis in prostate cancer cells involving activation of JNK-induced Bcl-2 phosphorylation and degradation.

Androgen-independent prostate cancers express high levels of Bcl-2, and this over-expression of Bcl-2 protects prostate cancer cells from undergoing apoptosis. Ursolic acid (UA) has demonstrated an anti-proliferative effect in various tumor types. The aim of this study is to evaluate the difference between UA-induced apoptosis in androgen-dependent prostate cancer cell line LNCaP cells and androgen-independent prostate cancer cell line LNCaP-AI cells and to reveal the molecular mechanisms underlying the apoptosis. We found that UA treatment in vitro can effectively induce apoptosis in LNCaP and LNCaP-AI cells. UA can overcome Bcl-2-mediated resistance to apoptosis in LNCaP-AI cells. Intrinsic apoptotic pathways can be triggered by UA treatment because c-Jun N-terminal kinase (JNK) is activated and subsequently provokes Bcl-2 phosphorylation and degradation, inducing activation of caspase-9. Although further evaluation is clearly needed, the present results suggest the potential utility of UA as a novel therapeutic agent in advanced prostate cancer.

[The clinical study for reducing bladder cancer recurrence after surgical treatment for renal pelvic carcinoma].

OBJECTIVE: To investigate the clinical methods for reducing bladder cancer recurrence after surgical treatment for renal pelvic carcinoma. METHODS: From October 1997 to December 2007, the data of 227 patients undergoing total nephroureterectomy for clinically localized transitional cell carcinoma of the renal pelvis with follow-up results were analyzed retrospectively, including 126 cases of male and 101 cases of female, and the age was 34 to 78 years old. There were 2 kinds of technique used in the dissection of bladder wall circumferentially around the ureteral orifice. Technique A was dissection along the ipsilateral ureter to the bladder wall. Technique B was dissection along the vas deferens to the bladder wall circumferentially around the ipsilateral ureteral orifice and division of the lateral vesical ligament to reach the seminal vesicle. Prophylactic intravesical chemotherapy included 3 method. Method 1 was intraoperative intravesical chemotherapy and then administrated once a week, 10 times in total. Method 2 was intraoperative intravesical chemotherapy and then administrated once a week from the 4(th) week after operation, 10 times in total. Method 3 was intravesical chemotherapy was given once a week from the 4(th) week after operation, 10 times in total. The time of follow-up was 1 to 10 years with regular cystoscopy. Chi-square test and Logistic regression were used to analyzed the recurrence rate of bladder cancer. RESULTS: Recurrence rate of bladder cancer was 27.8% (63/227). The recurrence rates of bladder cancer in patients using technique A and B were 18.0% (7/39) and 12.5% (3/24), respectively (P < 0.05). The postoperative recurrence rates of bladder cancer in patients using 3 kinds of intravesical chemotherapy regimen were 17.9% (11/67), 20.8% (10/48) and 33.3% (17/51), respectively. There was significant difference between the recurrence rates of patients using method 1 and method 3 intravesical chemotherapy (P < 0.05). CONCLUSION: Complete removal of the bladder mucosa circumferentially around the ureteral orifice, administration of the intraoperative intravesical chemotherapy instillation and instillation once a week may be a useful approach to reduce the recurrence of bladder cancer after operation for renal pelvic carcinoma.

Livin may serve as a marker for prognosis of bladder cancer relapse and a target of bladder cancer treatment.

OBJECTIVES: To evaluate the expression of Livin in bladder cancer, investigate its clinical and prognostic implications, and explore the effect of gene Livin transfection on the proliferation and apoptosis in bladder cancer cells. METHODS: The expression of Livinalpha and beta was detected in 48 bladder cancer samples (G(1) in 23 cases, G(2) in 17 cases, and G(3) in 8 cases. Of the 48 cases, 17 developed relapse) and 15 non-tumor bladder tissues by Western blot and reverse transcription PCR (RT-PCR). Livinalpha-pcDNA3.1(+) was constructed and transfected into T24, BIU-87 and EJ bladder cancer cells. The clone activity of the transfected cells was detected by colony formation analysis. MTT was used to determine the cell proliferation assay. Flow cytometry and acridine orange staining were used to examine apoptosis. Caspase 3 activity assay was also measured. RESULTS: Expression of Livinalpha, but not beta, was detected in 19 of the 48 bladder cancer samples; G(1) was 39.13%, G(2) and G(3) were 41.18% and 37.50%, respectively, which showed no significant (P > 0.05), but not in 15 non-tumor bladder tissues. The positive rate of Livinalpha was significant higher in relapse tumors (58.82%) than in primary tumors (29.03%) (P < 0.05). By the end of 2 years follow-up, the relapse rate in Livin positive patients was 68.42%, and 37.93% in Livin negative group. The difference between the two groups was significant (P < 0.05). Additionally, overexpression of Livinalpha clearly stimulated cell proliferation and inhibited chemical induced apoptosis in bladder cancer cells. CONCLUSIONS: Livin may serve as a promising marker to identify the relapse risk in bladder cancer, and targeting Livin could offer a therapeutic benefit in apoptosis-inducing treatment.

[Clinical research about treatment for adrenal incidentalomas].

OBJECTIVE: To explore the therapeutic methods of adrenal incidentalomas. METHODS: The data of 156 cases were analyzed retrospectively. RESULTS: The operation were performed in 151 cases, radiotherapy and chemotherapy in 1 case and follow up in 4 cases. The diameter of the tumors were 1.3-15.0 cm. Pathological results indicated that 34 cases were pheochromocytoma, 83 adrenal cortical adenoma, 5 adrenal cortical carcinoma, 3 metastases carcinoma, and 26 other benign tumors. One hundred and thirty-six cases were followed-up for 1-7 years. 3 cases of metastases carcinoma died in 1.5 years, 2 cases of cortical carcinoma died in 2.0 and 2.5 years for recurrence and metastases. One hundred and thirty-one cases survived healthy, 3 cases of them take orally dexamethasone for 1 year after post-operation. CONCLUSIONS: Surgical operations should be performed in malignant tumors, hypersecretion tumors, deuto-clinical adrenal cortical tumors, pheochromocytoma and those whose diameters of tumors are over 3 cm. But those whose tumors had non-hypersecretion and diameters are less than 3 cm should be followed up closely.

[Effects of gene Livin transfection affect on the apoptosis in bladder carcinoma cells].

OBJECTIVE: To investigate the effect of gene Livin transfection on the apoptosis of human bladder transitional cell carcinoma (BTCC) cells. METHODS: Target fragment containing Livin full-length cDNA was obtained from the breast cancer cells of the line MCF7. Vector pcDNA3. 1 (+)-Livin was constructed and transfected into the bladder transitional cell carcinoma (BTCC) cells of the line T24 [T24/ Livin+ cells]. Another T24 cells were transfected with the eukaryotic expression vectors pcDNA3.1 (+) [T24/pcDNA3.1 (+) cells]. T24 cells without transfection were used as blank control group. These T24 cells underwent G418 selection so as to screen the T24/Livin+ cells stably expressing the target fragment. RT-PCR was used to detect the Livin expression level in the transfected cells. After the cells were treated with mitomycin C (MMC) for 24 h, MTT method was used to detect the inhibition rate. Acridine orange (AO) staining was used to observe the apoptotic cells. The apoptotic rate was observed by flow cytometry. RESULTS: RT-PCR results indicated that expression of Livin was positive in the T24/Livin+ cells, while were negative in the T24/pcDNA3.1 (+) and T24 cells. After being treated with MMC for 24 h, the apoptotic rate of the T24/Livin+ cell was (8.7 +/- 1.5)%, significantly lower than those of the T24/pcDNA3.1 (+) cells and T24 cells [(21.4 +/- 2.3)% and (19.6 +/- 2.3)% respectively, both P < 0.01]. CONCLUSION: The gene Livin increases the anti-apoptosis ability of tumor cells and the cell apoptosis induced by chemotherapy.