MiR-520f promotes cell aggressiveness by regulating fibroblast growth factor 16 in hepatocellular carcinoma.

Cancer metastasis is a multistep cellular process, which has be confirmed one of mainly causes of cancer associated-death in hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) participate in tumorigenesis function as either tumor suppressor genes or oncogenes. In order to elaborate the critical miRNAs and their targets in HCC, we compared the differential expression of miRNA between HCC tissues and normal tissues. Microarray analysis revealed there were several significantly up-expression miRNAs in HCC, compared to normal solid tissue. Among them, the expression of miR-520f was the most over-expression in HCC cell lines than that in human normal liver cells LO2, as well as up-regulated in HCC than that in the corresponding normal tissues. Moreover, Kaplan Meier-plotter analyses revealed that higher miR-520f levels were negatively correlated with poor overall survival. By applying bioinformatics methods to identify the targeting genes of miRNA, we demonstrated that fibroblast growth factor 16 (FGF16) was the miR-520f-targeted gene. Meanwhile, FGF16 exhibited similar expression patterns to miR-520f in HCC. Forced miR-520f expression accelerated HCC cells proliferation and aggressiveness in vitro and in vivo, whereas down-regulation of miR-520f caused an opposite outcome. Moreover, over-expression of FGF16 was closely related to the metastatic potential of HCC cells. Herein, we also confirmed that ectopic expression of FGF16 in HCC cells promoted proliferation, colony formation, and increased migration, invasion of HCC cells in vitro. Collectively, our results indicated that over-expression of miR-520f and FGF16 was positively associated with aggressive phenotypes and poor survival of patients with HCC, and miR-520f promoted HCC aggressive phenotypes by regulating the expression of FGF16. MiR-520f may be employed as a prognostic factor and therapeutic target for HCC.

Long noncoding RNA CCAT1 promotes hepatocellular carcinoma progression by functioning as let-7 sponge.

BACKGROUND: Long noncoding RNAs (lncRNAs) have been identified as having functional roles in cancer biology and are deregulated in many cancers. The present study aimed to determine the expression, roles and functional mechanisms of a long noncoding RNA CCAT1 in the progression of hepatocellular carcinoma (HCC). METHODS: CCAT1 expression levels in 66 pairs of HCC tissues and pair-matched noncancerous hepatic tissues were tested by real-time PCR. The effects of CCAT1 on HCC cells proliferation and migration were assessed using in vitro cell proliferation and migration assays. A computational screen of microRNAs (miRNAs) target sites in CCAT1 was conducted to search for specific miRNAs binding to CCAT1. The specific binding between CCAT1 and miRNAs was confirmed by RNA immunoprecipitation assay combined with luciferase reporter assay. RESULTS: CCAT1 levels are markedly increased in HCC tissues compared with pair-matched noncancerous hepatic tissues. Up-regulation of CCAT1 is correlated with tumor size, microvascular invasion, AFP and poor prognosis. CCAT1 promotes the proliferation and migration of HCC cells. CCAT1 functions as a molecular sponge for let-7, antagonizes its functions, and leads to the de-repression of its endogenous targets HMGA2 and c-Myc. The effect of CCAT1 on HCC cell proliferation and migration is dependent upon its competitively binding to let-7. CONCLUSIONS: These data suggest that CCAT1 plays a pivotal role in HCC progression via functioning as let-7 sponge, and implicate the potential application of CCAT1 for the prognosis and treatment of HCC.

Hybrid eccrine gland and hair follicle hamartoma: a new entity of adnexal nevus.

Eccrine nevus shows increase in number or size of eccrine glands, whereas hair follicle nevus is composed of densely packed normal vellus hairs, and eccrine-pilar angiomatous nevus reveals increase of eccrine, pilar, and angiomatous structures. No case with increased number of both eccrine glands and hair follicles only in the dermis has been previously reported. A 10-month-old girl presented with cutaneous hamartoma with overlying skin hyperpigmentation on her left hypochondrium since 3 months of age, in whom the lesion was completely excised. Histopathology demonstrated evidently increased number of both eccrine glands and hair follicles in the dermis with reactive hyperplasia of collagen fibers. No recurrence occurred after the tumor was completely excised. A term "hybrid eccrine gland and hair follicle hamartoma" is proposed for this unique lesion.

[Prognostic value of metastatic lymph node ratio in gastric cancer patients undergoing radical gastrectomy].

OBJECTIVE: To assess the prognostic value of metastatic lymph node ratio in gastric cancer patients undergoing radical gastrectomy (D2). METHODS: Prognostic analysis of 1042 gastric cancer patients undergoing radical gastrectomy (D2) was performed based on metastatic lymph node ratio (MLR), the N staging in the 6th and 7th edition of UICC staging system respectively. Homogeneity, discriminatory ability, and gradient monotonicity of these three staging methods were compared using linear trend χ(2), likelihood ratio χ(2) statistics and Akaike information criterion (AIC) calculations, respectively. The area under the ROC curve (AUC) was calculated to compare the prognostic value of these three staging methods. RESULTS: The 5-year survival rate of 1042 patients was 47.5%. The metastatic lymph node ratio (P<0.01) and N staging of the 7th edition UICC (P<0.05) were independent prognostic factors according to univariate and multivariate analyses. The AUC was 0.754 in MLR staging group, higher than that in N staging of the 6th (0.692) and 7th (0.705) edition of UICC group. Compared to the 6th and 7th edition of UICC N staging group, homogeneity and linear curve were better and AIC value was lower in MLR staging group (7240.017 vs. 7364.073 and 7325.731). CONCLUSION: Prognostic value of MLR staging is better than that of UICC N staging for patients undergoing radical gastric cancer resection. The MLR staging can be a new method of lymph node staging for gastric cancer patients.

Superiority of metastatic lymph node ratio to the 7th edition UICC N staging in gastric cancer.

AIM: To compare and evaluate the appropriate prognostic indicators of lymph node basic staging in gastric cancer patients who underwent radical resection. METHODS: A total of 1042 gastric cancer patients who underwent radical resection and D2 lymphadenectomy were staged using the 6th and 7th edition International Union Against Cancer (UICC) N staging methods and the metastatic lymph node ratio (MLNR) staging. Homogeneity, discriminatory ability, and gradient monotonicity of the various staging methods were compared using linear trend χ(2), likelihood ratio χ(2) statistics, and Akaike information criterion (AIC) calculations. The area under the curve (AUC) was calculated to compare the predictive ability of the aforementioned three staging methods. RESULTS: Optimal cut-points of the MLNR were calculated as MLNR0 (0), MLNR1 (0.01-0.30), MLNR2 (0.31-0.50), and MLNR3 (0.51-1.00). In univariate, multivariate, and stratified analyses, MLNR staging was superior to the 6th and 7th edition UICC N staging methods. MLNR staging had a higher AUC, higher linear trend and likelihood ratio χ(2) scores and lower AIC values than the other two staging methods. CONCLUSION: MLNR staging predicts survival after gastric cancer more precisely than the 6th and 7th edition UICC N classifications and should be considered as an alternative to current pathological N staging.

[Laparoscopic versus open appendectomy in patients with chronic appendicitis].

OBJECTIVE: To compare the advantages and disadvantages of laparoscopic versus open appendectomy in patients with chronic appendicitis. METHODS: Two hundred twenty- four patients were divided into laparoscopic group (n=98) and open appendectomy group (n=126) according to individual willing. Prospective non- randomized study was performed to compare the operative time, operative bleeding, hospitalization time, the discovery and management concerned in operation. Abdominal pain in these chronic appendicitis cases was followed up. RESULTS: The operative time was (54.8+/-21.8) min in open group and (51.8+/-18.0) min in laparoscopic group (t=0.80,P > 0.05). The operative bleeding was (18.6+/-23.3) ml in open group and (9.8+/-4.7) ml in laparoscopic group (t=3.13, P < 0.05). The hospitalization time was (8.9+/-5.3) d in open group and (6.8+/-3.0) d in laparoscopic group (t=2.66,P < 0.05). Twenty- five cases had abdominal adhesion in laparoscopic group, including 9 cases of adhesion around appendix, 6 cases of adhesion between ileocecum and anterior or lateral abdominal wall, 4 cases of adhesion between epiploon and abdominal wall or intestines, 6 cases of adhesion around colon and others. All adhesion had been dissected. Fourteen cases adhesion around appendix had been discovered in 126 cases of open group and dissected (chi(2) =7.95,P < 0.05). In follow- up research, 24 cases still had chronic abdominal pain in 98 case of open group, and 9 cases had chronic abdominal pain in 87 of laparoscopic group, the difference was significant (chi(2)=6.29,P < 0.05). CONCLUSION: The laparoscopic appendectomy possesses more advantages in treating chronic appendicitis and can decrease the incidence of chronic abdominal pain after operation.

Changes in the level of serum liver enzymes after laparoscopic surgery.

AIM: The purpose of this study was to investigate the effect of laparoscopic surgery on liver function in humans and the possible mechanisms behind such effect. METHODS: Blood samples from 286 patients who underwent laparoscopic cholecystectomy (LC) and 40 patients who underwent open cholecystectomy (OC) were tested for liver function by measuring the level of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) before and after the operations. The same tests were also applied to 18 laparoscopic colorectal cancer resection (LCR) patients and 23 open colorectal cancer resection (OCR) patients to determine whether CO(2) pneumoperitoneum could alter the serum liver enzymes. RESULTS: The level of serum ALT and AST increased significantly during the first 48 hours post operations in both LC and LCR patients. However, no significant change of the serum liver enzymes was detected in both OC and OCR patients. As a result, there was statistically significant difference in change of both ALT and AST levels between LC and OC patients and LCR and OCR patients, respectively. By the 7(th) day post operation, the level of both enzymes returned to normal values in LC, OC and OCR patients except LCR patients whose enzymes remained at a higher level. CONCLUSION: Transient elevation of hepatic transaminases occurred after laparoscopic surgery. The major causative factor seemed to be the CO(2) pneumoperitoneum. In most of the laparoscopic surgery patients, the transient elevation of serum liver enzymes showed no apparent clinical implications. However, if preoperative liver function was very poor, laparoscopic surgery may not be the best choice for the treatment of patients with certain abdominal diseases.

Polyadenylation can regulate ColE1 type plasmid copy number independently of any effect on RNAI decay by decreasing the interaction of antisense RNAI with its RNAII target.

Replication of ColE1-type plasmids is regulated by RNAI, an antisense RNA that interacts with the replication pre-primer, RNAII. Exonucleolytic attack at the 3' end of RNAI is impeded in pcnB mutant bacteria, which lack poly(A) polymerase I-the principal RNA polyadenylase of E. coli; this leads to accumulation of an RNAI decay intermediate (RNAI(-5)) and dramatic reduction of the plasmid copy number. Here, we report that polyadenylation can also affect RNAI-mediated control of plasmid DNA replication by inhibiting interaction of RNAI(-5) with RNAII. We show that mutation of the host pcnB gene profoundly affects the plasmid copy number, even under experimental conditions that limit the effects of polyadenylation on RNAI(-5) decay. Moreover, poly(A) tails interfere with RNAI/RNAII interaction in vitro without producing any detectable alteration of RNAI secondary structure. Our results establish the existence of a previously undetected mechanism by which RNA polyadenylation can control plasmid copy number.