Role of a novel circRNA-CGNL1 in regulating pancreatic cancer progression via NUDT4-HDAC4-RUNX2-GAMT-mediated apoptosis.

BACKGROUND: Pancreatic cancer (PC) is an extremely malignant tumor with low survival rate. Effective biomarkers and therapeutic targets for PC are lacking. The roles of circular RNAs (circRNAs) in cancers have been explored in various studies, however more work is needed to understand the functional roles of specific circRNAs. In this study, we explore the specific role and mechanism of circ_0035435 (termed circCGNL1) in PC. METHODS: qRT-PCR analysis was performed to detect circCGNL1 expression, indicating circCGNL1 had low expression in PC cells and tissues. The function of circCGNL1 in PC progression was examined both in vitro and in vivo. circCGNL1-interacting proteins were identified by performing RNA pulldown, co-immunoprecipitation, GST-pulldown, and dual-luciferase reporter assays. RESULTS: Overexpressing circCGNL1 inhibited PC proliferation via promoting apoptosis. CircCGNL1 interacted with phosphatase nudix hydrolase 4 (NUDT4) to promote histone deacetylase 4 (HDAC4) dephosphorylation and subsequent HDAC4 nuclear translocation. Intranuclear HDAC4 mediated RUNX Family Transcription Factor 2 (RUNX2) deacetylation and thereby accelerating RUNX2 degradation. The transcription factor, RUNX2, inhibited guanidinoacetate N-methyltransferase (GAMT) expression. GAMT was further verified to induce PC cell apoptosis via AMPK-AKT-Bad signaling pathway. CONCLUSIONS: We discovered that circCGNL1 can interact with NUDT4 to enhance NUDT4-dependent HDAC4 dephosphorylation, subsequently activating HDAC4-RUNX2-GAMT-mediated apoptosis to suppress PC cell growth. These findings suggest new therapeutic targets for PC.

Reverse shoulder arthroplasty vs. hemiarthroplasty for the treatment of osteoporotic proximal humeral fractures in elderly patients: A systematic review and meta­analysis update.

The present meta-analysis was conducted to compare the safety and effectiveness of reverse shoulder arthroplasty (RSA) and hemiarthroplasty (HA) in the treatment of osteoporotic proximal humeral fractures in elderly patients. The Embase, Pubmed Central, Cumulative Index to Nursing and Allied Health Literature, ProQuest Dissertations and Theses, Cochrane Library and Chinese Biomedical databases were searched between January 2009 and January 2022 to identify relevant studies. According to the search strategy, a total of 210 associated studies were retrieved and 16 were finally included. Review Manager 5.4 software was used for the data analysis. This study indicated that patients in the RSA group had significantly improved treatment outcomes compared with patients in the HA group, as assessed by Constant-Murley Shoulder Outcome Score (95% CI, 1.69-3.76; P<0.001), American Shoulder and Elbow Surgeons score (95% CI, 11.81-24.88; P<0.001) and shoulder range of motion (ROM; 95% CI, 3.41-9.07; P<0.001). However, the HA group was superior to the RSA group in terms of the Oxford Shoulder score (95% CI, 2.89-11.11; P<0.001). There was no significant statistical difference between the two groups in terms of the Disabilities of the Arm, Shoulder and Hand score and complications. Overall, for the treatment of osteoporotic proximal humeral fractures in the elderly, the RSA group had improved postoperative ROM and functional scores compared with the HA group, without significant difference in the incidence of complications. However, HA remains a safe and reliable treatment option.

Trichostatin A potentiates genistein-induced apoptosis and reverses EMT in HEp2 cells.

Genistein and trichostatin A (TSA) are two chemotherapeutic compounds with antitumor effects in different types of cancer cell. However, the effects of genistein and TSA on the HEp­2 laryngeal cancer cell line remain to be fully elucidated. In the present study, it was found that genistein and TSA inhibited cell growth and cell migration, and promoted apoptosis in the HEp­2 laryngeal cancer cell line. The HEp­2 cells were treated with genistein, TSA or the two compounds in combination. Cell proliferation and apoptosis were measured using an MTT assay, Annexin V/propidium iodide staining and a TUNEL assay. Cell invasion was determined using a Matrigel­based Transwell assay. Western blotting was used to examine the activation of the Akt pathway and the expression levels of pro­or anti­apoptotic proteins. Treatment with either genistein or TSA alone mildly inhibited cell viability, growth and invasion, and induced the apoptosis of the laryngeal cancer cells, whereas more marked effects were observed in the cells treated with the combination of the two compounds. In addition, genistein reversed endothelial growth factor­induced epithelial­mesenchymal transition (EMT) in the HEp­2 cells, the effect of which were was further increased by joint application with TSA. Treatment of the HEp­2 cells with genistein and TSA led to a significant reduction in the phosphorylation of Akt and activation of its downstream target, and resulted in peroxisome proliferator­activated receptor­Î³ cleavage, increased expression of B cell lymphoma­2 (Bcl­2)­associated X protein and reduced the expression of Bcl­2. In conclusion, the present study demonstrated that, with the involvement of TSA, genistein exhibited substantial advantages in inhibiting laryngeal carcinoma cell growth, invasion and EMT, and induced apoptosis, compared with genistein treatment alone, which occurred through the regulation of Akt activation and the apoptotic pathway.

[Relationship of local recurrence with the expression of Survivin and MMP-2 in laryngeal carcinoma and its surgical margins].

OBJECTIVE: To explore the relationship of the local recurrence with the expression of protein Survivin and MMP-2 in the primary lesions and the surgical margins of laryngeal carcinoma. METHOD: The primary lesions and the surgical margins of laryngeal carcinoma of 48 patients were made into serial sections. Immunochemical methods was used to detect the expression of protein Survivin and MMP-2 in the primary lesion and the surgical margins of laryngeal carcinoma of 48 patients. RESULT: The positive expression for Survivin and MMP-2 in the primary lesion was 70.83% (34/48) and 66.67% (32/48) respectively, and the positive expression of Survivin and MMP-2 in the surgical margins of laryngeal carcinoma was 47.92% (23/48) and 37.50% (18/48), which in the primary lesion was significantly higher than those of the surgical margins of laryngeal carcinoma (P < 0.05). The recurrence rates of primary lesion positive for Survivin (34 cases) and MMP-2 (32 cases) were 26.47% (9/34) and 25.00% (8/32), which were higher than negative for them 7.14%(1/14) and 12.50% (2/16) (P > 0.05). The recurrence rates of those with Survivin (23 cases) and MMP-2 (18 cases) positive surgical margins were 34.78% (8/23) and 38.89% (7/18) respectively, which were significantly higher than those with negative ones 8.00% (2/25) and 10.00% (3/30) (P < 0.05). Logistic analysis showed that the expression of Survivin and MMP-2 protein in the surgical margins of laryngeal carcinoma was positively associated with the recurrence rates. CONCLUSION: Laryngeal carcinoma patients with Survivin-positive or MMP-2-positive margin would have a higher recurrence rate. Survivin and MMP-2 protein can be used as biomarkers for local recurrence of laryngeal carcinoma after operation.

[Relationship between expression of MMP-2 and prognosis in human laryngeal squamous cell carcinoma].

OBJECTIVE: In order to evaluate the potential of matrix metalloproteinase 2(MMP-2) as a prognostic factor for human laryngeal squamous cell carcinoma (HLSCC). METHOD: Seventy-three surgical specimens from patients with HLSCC were reviewed retrospectively regarding MMP-2 expression via immunohistochemistry. Immunostaining was performed using a streptavidin-biotin peroxidase complex technique. The patients were followed-up till June 2014 and the relationship between MMP-2 and clinical data including age, gender, metastasis, clinical type, pathological type, lymph node metastasis and prognosis were analyzed using SPSS 19.0. RESULT: The positive expression rate of MMP-2 in 73 patients was 57.53% (42/73). Kaplan-Meier analysis demonstrated statistically significant difference for 5-year overall survival rate between the group with positive and negative MMP-2 expression,the 5-year overall survival rate were 76.0% and 57.5% respectively in the group with negative and positive MMP-2 expression. The site of the primary tumor, clinical stage, lymph node metastasis and T grade were related to the prognosis of HLSCC (P were 0.002, 0.009, 0.034 and 0.001 respectively), and there was no significant correlation between age, sex, pathological differentiation and prognosis of HLSCC. CONCLUSION: MMP-2 was related with worse overall disease survival and could be considered as a potential marker of poor prognosis.