Correlation of miRNA-21 and blood Cr levels with tumor infiltration and distant metastasis in renal cancer patients.

The object of this study was to explore the correlation analysis between miRNA-21 and blood Cr levels with tumor invasion and distant metastasis in renal cancer patients. For this purpose 49 cases of renal cancer patients treated in our hospital from February 2018 to March 2020 were selected as the study group, and another 165 cases of renal benign tumors that were pathologically confirmed in our hospital during the same period were selected as the control group. MiRNA-21 and blood Cr levels, miRNA-21 and blood Cr levels at different stages, and miRNA-21 and blood Cr levels when tumor invasion and distant metastasis were present were compared between the two groups. Results showed that compared with the control group, the levels of miRNA-21 and blood Cr in the study group increased, the difference was significant (P < 0. 05); compared with stage I patients, the levels of miRNA-21 and blood Cr in stage II patients increased, compared with stage II patients, the levels of miRNA-21 and blood Cr in stage III patients increased, compared with stage III patients, the levels of miRNA-21 and blood Cr in stage IV patients increased, the difference was significant Compared with the case without tumor invasion, the levels of miRNA-21 and blood Cr in the case of tumor invasion were increased, the difference was statistically significant (P < 0. 05); compared with the case without distant metastasis, the levels of miRNA-21 and blood Cr in the case of tumor distant metastasis were increased, the difference was significant (P < 0. 05) When distant metastasis, miRNA-21 and blood Cr levels increased significantly, which showed that miRNA-21 and blood Cr levels were positively correlated with tumor invasion and distant metastasis; compared with the control group, TIMP1, TIMP2, MACC1 protein expression in the study group increased, and the three showed a positive correlation, the difference was significant (P < 0. 05). It is concluded when renal cancer patients were tested, we found that miRNA-21 and blood Cr levels were abnormally increased, and the two had a certain correlation with renal cancer tumor invasion and distant metastasis, which showed a positive correlation.

LncRNA GAS5 enhances tumor stem cell-like medicated sensitivity of paclitaxel and inhibits epithelial-to-mesenchymal transition by targeting the miR-18a-5p/STK4 pathway in prostate cancer.

The onset of prostate cancer (PCa) is often hidden, and recurrence and metastasis are more likely to occur due to chemotherapy resistance. Herein, we identified downregulated long noncoding RNA (lncRNA) growth arrest-specific 5 (GAS5) in PCa that was associated with metastasis and paclitaxel resistance. GAS5 acted as a tumor suppressor in suppressing the proliferation and metastasis of paclitaxel-resistant PCa cells. GAS5 overexpression in vivo inhibited the tumor growth of xenografts and elevated PCa sensitivity to paclitaxel. Combination of GAS5 and paclitaxel treatment showed great potential in PCa treatment. Moreover, mechanistic analysis revealed a novel regulatory network of GAS5/miR-18a-5p/serine/threonine kinase 4 (STK4) that inhibits epithelial-to-mesenchymal transition (EMT) and enhances tumor stem cell-like-mediated sensitivity to paclitaxel in PCa. These findings provide a novel direction for the development of a potential adjunct to cancer chemotherapy that aims to improve the sensitivity of chemotherapy drugs in PCa.

Maternal embryonic leucine zipper kinase serves as a potential prognostic marker and leads to sorafenib chemoresistance modified by miR-142-5p in hepatocellular carcinoma.

BACKGROUND: Chemotherapy is an important treatment strategy for advanced hepatocellular carcinoma (HCC). Sorafenib is a first-line systemic drug that has been commonly used clinically for patients with advanced HCC. However, the high resistance rate of sorafenib in HCC patients often hinders its long-term efficacy. Therefore, it is vital to reveal the molecular mechanisms of sorafenib resistance in patients with HCC. METHODS: In current study, we screened out fourteen genes that over-expressed in HCC specimens through integrative bioinformatics analysis. Here, maternal embryonic leucine zipper kinase (MELK) was highlighted as one of the most probable molecules. The Database for Annotation Visualization and Integrated Discovery (DAVID) program was utilized for functional pathway enrichment analysis. Real-time PCR (RT-PCR) and western blot were used to examine the expression levels of MELK. CCK-8, transwell, colony formation assays and flow cytometry were used to detect cell proliferation, the cell cycle. The dual luciferase assays were performed to study the targeting relationship between MELK and miR-142-5p. RESULTS: MELK expressions were correlated significantly with cell proliferation by regulating cell cycle and DNA replication. High MELK expression in patients with HCC indicated a poor prognosis both the overall and diseases free survival rates. MELK knockdown suppresses cell proliferation, migration and invasion in vitro. miR-142-5p regulates MELK expression through binding to the complementary sequence in the 3'-UTR regions. MELK knockdown enhances sensitivity of sorafenib in HCC sorafenib-resistant (HCC/SR) cells. CONCLUSIONS: MELK may serve as a potential prognostic marker in HCC and MELK knockdown enhanced sensitivity of HepG2/SR cells to sorafenib treatment. Our findings suggest that MELK/miR-142-5p axis could be a potentially therapeutic target for reversing the sorafenib resistance in HCC treatment.

TRIM13 inhibits cell migration and invasion in clear-cell renal cell carcinoma.

TRIM13, a member of the TRIM family, is a RING domain containing E3 ubiquitin ligase which plays critical roles in diverse cellular processes including cell death, cancer and antiviral immunity. However, its expression and molecular mechanism on renal cell carcinoma (RCC) have not been characterized. This study explored the clinical significance and biological function of TRIM13 in human RCC. Western blot analyses and Immunohistochemical were performed in RCC tissues. The clinical relevance of TRIM13 in RCC was evaluated by immunohistochemical staining using tissue microarray. The role of TRIM13 in migration was studied in renal cell carcinoma cell lines of 786-O through knocking down TRIM13 with siRNA and over-expression of TRIM13. The regulation of TRIM13 on migration and invasion were determined by wound-healing and transwell assays. Western blot analyses showed that TRIM13 expression was dramatically decreased in RCC tissues compared with adjacent non-tumorous tissues. Up-regulation of TRIM13 in 786-O cells resulted in decreased NF-kB, MMP-9 and p-AKT levels and the capability for migration and invasion. In contrast, the ectopic expression of TRIM13 decreased the migration and invasion ability of 786-O cells. These findings indicate that TRIM13 decreases RCC metastasis and invasion may serve as a candidate RCC prognostic marker and a potential therapeutic target.

[Predictive factors for clinically significant elevation of post-prostatectomy Gleason score in patients with biopsy Gleason score ≤7].

OBJECTIVE: To investigate the prognostic factors for clinically significant increase in post-prostatectomy Gleason score (pGS) in patients with biopsy Gleason score (bGS) ≤7. METHODS: This retrospective study included 170 cases of prostate cancer treated by radical prostatectomy in our hospital from January 2010 to December 2017. We analyzed the clinical and pathological data on the patients, including the age, preoperative serum tPSA, fPSA, fPSA / tPSA, prostate volume, PSA density (PSAD), and positive puncture rate of the patients with clinically significant elevation of pGS, as well as the possible factors for clinically significant pGS increase in patients with bGS = 7 and those with bGS ≤ 6. RESULTS: The pGS was found consistent with the bGS in 95 (55.9%) of the 170 patients, decreased in 11 (6.5%) and increased in 64 (37.6%). Among those with elevated pGS, 55 (32.4%) were shown with and the other 9 (5.3%) without clinical significance. Clinically significant escalation of pGS was markedly correlated with the positive puncture rate in the patients with bGS = 7 (P = 0.021) and with the age (P = 0.018) and PSAD (P = 0.033) of those with bGS ≤ 6. ROC curve analysis further showed the positive puncture rate > 0.528 in the patients with bGS = 7 and a higher risk of clinically significant pGS increase in those aged > 64.5 years with bGS ≤ 6 and PSAD > 0.267 µg/(L·g). CONCLUSIONS: Clinically significant elevation of pGS is correlated with the rate of positive punctures in prostate cancer patients with bGS = 7 and with age and PSAD in those with bGS ≤ 6.

The Impact of Adjuvant Therapy on Survival and Recurrence Patterns in Women With Early-Stage Uterine Carcinosarcoma: A Multi-institutional Study.

OBJECTIVE: The aim of the study was to characterize the impact of adjuvant therapy on survival in women with stage I/II uterine carcinosarcoma after primary surgery. METHODS: We reviewed records of 118 consecutively treated women with 2009 International Federation of Gynecology and Obstetrics stage I/II uterine carcinosarcoma who underwent hysterectomy between 1990 and 2014 at 4 academic institutions. Patients were categorized by adjuvant treatment group into observation, chemotherapy only, radiation only, and combined chemotherapy and radiation. Survival analyses were conducted using Kaplan-Meier and Cox proportional hazards models. RESULTS: Median follow-up was 28 months (range, 1-244 months). Lymphadenectomy was performed in 94 patients (80%). Postoperative management included observation (n = 37 [31%]), chemotherapy alone (n = 19 [16%]), radiation therapy (RT) alone (n = 24 [20%]), and combined RT and chemotherapy (n = 38 [32%]). Radiation therapy modality included vaginal brachytherapy in 22 patients, pelvic external beam RT in 21 patients, and combination in 19 patients. In 58% of women, chemotherapy consisted of carboplatin/paclitaxel. Median overall survival for all women was 97 months. On univariate analysis, adjuvant treatment group was associated with improved overall survival (hazard ratio [HR], 0.74; confidence interval [CI], 0.58-0.96; p = 0.02), freedom from vaginal recurrence (HR, 0.55; CI, 0.37-0.82]; p = 0.004), and freedom from any recurrence (HR, 0.70; CI, 0.54-0.92; p = 0.01). Pairwise comparisons demonstrated a significant benefit to chemoradiation over other adjuvant treatments. Adjuvant treatment group remained a significant covariate for all 3 end points on multivariate analysis as well. In addition, lymphadenectomy improved overall survival on multivariate analysis (HR, 0.24; CI, 0.09-0.61; p = 0.003). Of patients under observation only who had a recurrence, 8 (44%) of 18 had a recurrence in the vagina as the sole site of recurrence. By contrast, of women who received vaginal brachytherapy, significantly fewer had a recurrence in the vagina (1/42 [2.3%]; p < 0.003, log-rank test). CONCLUSIONS: In women with early-stage uterine carcinosarcoma, our data suggest superior survival end points with combined RT and chemotherapy. The frequency of vaginal recurrence suggests a role for incorporating vaginal brachytherapy in the adjuvant management of this disease.

AP-2gamma induces p21 expression, arrests cell cycle, and inhibits the tumor growth of human carcinoma cells.

Activating enhancer-binding protein 2gamma (AP-2gamma) is a member of the developmentally regulated AP-2 transcription factor family that regulates the expression of many downstream genes. Whereas the effects of AP-2alpha overexpression on cell growth are fairly well established, the cellular effects of AP-2gamma overexpression are less well studied. Our new findings show that AP-2gamma significantly upregulates p21 mRNA and proteins, inhibits cell growth, and decreases clonogenic survival. Cell cycle analysis revealed that forced AP-2gamma expression induced G1-phase arrest, decreased DNA synthesis, and decreased the fraction of cells in S phase. AP-2gamma expression also led to cyclin D1 repression, decreased Rb phosphorylation, and decreased E2F activity in breast carcinoma cells. AP-2gamma binding to the p21 promoter was observed in vivo, and the absence of growth inhibition in response to AP-2gamma expression in p21(-/-) cells demonstrated that p21 caused, at least in part, AP-2-induced cell cycle arrest. Finally, the tumor growth of human breast carcinoma cells in vivo was inhibited by the expression of AP-2gamma relative to empty vector-infected cells, suggesting that AP-2gamma acts as a tumor suppressor. In summary, expression of either AP-2gamma or AP-2alpha inhibited breast carcinoma cell growth; thus, these genes may be therapeutic targets for breast cancer.