Rapid dissolution microneedle based on polyvinyl alcohol/chitosan for local oral anesthesia.

At present, the main clinical methods of oral local anesthesia are direct injection of anesthetic and surface ointment. However, the pain and fear caused by the injection, the discomfort of topical anesthetic creams, and the scour and moist oral environment during the procedure pose great challenges to oral anesthesia. Herein, we designed a Lido-PVP/PVA DMNP microneedle (MN) for oral local anesthesia. The microneedle tip was consisted of Polyvinylpyrrolidone/Polyvinyl alcohol (PVP/PVA), which can quickly dissolve and release the lidocaine hydrochloride (Lido) drug within 5 min to achieve rapid anesthesia. The backing was composed of polyvinyl alcohol/chitosan (PVA/CS), and its excellent adhesion can overcome saliva erosion and anchor firmly to the oral mucosa, significantly improving the utilization rate of drugs, as well as the patient compliance. MNs have good mechanical properties for tissue insertion while possessing high drug loading (3 mg/MNs). Von Frey tests proved that MNs showed a faster and more effective local anesthetic effect (anesthesia takes effect at 5 min) compared to cream (anesthesia takes effect at 30 min). In addition, the excellent biocompatibility and no skin irritation endowed Lido-PVP/PVA DMNP MNs a great potential for oral local anesthesia in the oral cavity.

The ATO/miRNA-885-5p/MTPN axis induces reversal of drug-resistance in cholangiocarcinoma.

PURPOSE: Cholangiocarcinoma (CCA) is the second most malignant tumor of the hepatobiliary system. Due to its cumbersome early diagnosis and rapid progression, chemotherapy has become the main treatment option. Primary drug resistance is a major cause of the poor efficacy of chemotherapeutic drugs. Therefore, it is considered urgent to explore new drugs to overcome primary drug resistance of CCA. METHODS: Western blot and qRT-PCR assays were used to assess the expression of myotrophin (MTPN) and microRNA-885-5p (miR-885-5p) in CCA tissues and cells. The viability of CCA cells treated with arsenic trioxide (ATO), 5-fluorouracil (5-Fu) and cisplatin (CDDP) was analyzed using a CCK-8 assay. A luciferase reporter assay was used to assess the interaction between miR-885-5p and MTPN. Kaplan-Meier analyses were used for survival assessments. RESULT: We found that ATO can reduce the resistance of CCA cells to 5-Fu and CDDP and promote the killing effect of 5-Fu and CDDP. Low-dose ATO showed an anti-drug-resistance effect through up-regulation of the expression of miR-885-5p. Combined with sequencing results and database predictions, we found that MTPN may serve as a direct target of miR-885-5p. After MTPN knockdown, the sensitivity of CCA cells to 5-FU and CDDP was increased. Finally, we found that ATO can reverse chemotherapy resistance induced by overexpression of MTPN. CONCLUSION: Our data indicate that the ATO/miR-885-5p/MTPN axis may serve as a target for improving the sensitivity of CCA cells to chemotherapy.

The diagnostic value of exosomal miRNAs in human bile of malignant biliary obstructions.

BACKGROUND: Diagnosis of malignant biliary obstruction is complicated and lacks accuracy. Exosomes may be secreted by malignant tumors; intact miRNAs from exosomes might serve as potential biomarkers for the disease. AIM: To identify exosomal microRNAs in human bile among benign and malignant biliary obstructions. METHODS: Bile samples were collected from patients undergoing therapeutic endoscopic retrograde cholangiopancreatography for biliary obstruction. Exosome microRNAs were determined by RNA-sequencing in the discovery cohort, which comprising benign (n = 5) cases and malignant biliary obstruction (n = 5) cases. Then, the diagnostic performance of the two up-regulated microRNAs (mir-483-5p and mir-126-3p) of bile exosomes was verified by analysis of 82 patients with a diagnosis of malignant (n=37) or nonmalignant (n=45) biliary obstruction. RESULTS: In both cohorts, the expressions of mir-483-5p and mir-126-3p were significantly higher in bile exosomes samples from patients with malignant biliary obstructions than controls. In the verification cohort, the two miRNAs can distinguished the benign and malignant groups with high diagnostic accuracy and specificity; the diagnostic values of the two microRNAs were better than serum carbohydrate antigen 19-9 (CA19-9), area under the curve (AUC) were 0.81 and 0.74. CONCLUSION: The expression of exosomal mir-483-5p and mir-126-3p in the bile samples discriminates between patients with malignant and nonmalignant biliary obstructions. CLINICAL TRIAL REGISTRATION NO: NCT03102268.

Emerging roles of long noncoding RNAs in cholangiocarcinoma: Advances and challenges.

Cholangiocarcinoma (CCA), a cancer with a relatively low incidence rate, is usually associated with poor prognosis. Current modalities for the diagnosis and treatment of CCA patients are still far from satisfactory. In recent years, numerous long noncoding RNAs (lncRNAs) have been identified as crucial players in the development of various cancers, including CCA. Abnormally expressed lncRNAs in CCA, regulated by some upstream molecules, significantly influence the biological behavior of tumor cells and are involved in tumor development through various mechanisms, including interactions with functional proteins, participation in competing for endogenous RNA (ceRNA) regulatory networks, activation of cancer-related signaling pathways and epigenetic modification of gene expression. Furthermore, several lncRNAs are closely associated with the clinicopathological features of CCA patients, and are promising biomarkers for diagnosing and prognostication of CCA. Some of these lncRNAs play an important role in chemotherapy drug resistance. In addition, lncRNAs have also been shown to be involved in the inflammation microenvironment of CCA and malignant outcome of CCA risk factors, such as cholestatic liver diseases. In view of the difficulty of diagnosing CCA, more attention should be paid to detectable lncRNAs in the serum or bile. This review summarizes the recent knowledge on lncRNAs in CCA and provides a new outlook on the molecular mechanisms of CCA development from the perspective of lncRNAs. Moreover, we also discussed the limitations of the current studies and differential expression of lncRNAs in different types of CCA.

Endoscopic retrograde cholangiopancreatography in elderly patients: Difficult cannulation and adverse events.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is a valuable therapeutic technique for pancreatobiliary diseases, and its application in the elderly is no longer limited. However, a higher incidence of procedure difficulty and periprocedural adverse events might be expected in elderly patients due to the presence of other medical disorders and the poor general condition of this population. AIM: To evaluate the incidence, causes, and management of difficult biliary cannulation during ERCP in elderly patients and the role of difficult cannulation as a risk factor for adverse events. METHODS: A total of 614 patients who underwent ERCP during the study period were prospectively studied and divided into two groups based on their age. One hundred and forty-six patients were aged 80 years or older and 468 patients were aged less than 80 years. The primary outcome measurements were cannulation difficulty, cannulation success rate, ERCP procedure time, and related adverse events. RESULTS: There was no difference in the incidence of difficult cannulation among the two groups (32.9% vs 34.4%, P = 0.765), as well as in the cannulation success rate (96.6% vs 96.8%, P = 0.54). The cannulation techniques were shown to be safe and efficient in achieving successful cannulation. Logistic regression analysis showed that patients aged 80 years or older were not associated with increased adverse events; however, difficult cannulation cases [adjusted odds ratio (AOR) = 3.478; 95% confidence interval (CI): 1.877-6.442; P < 0.001] and patients with Charlson Comorbidity Index ≥ 2 (AOR = 1.824; 95%CI: 0.993-3.349; P = 0.045) were more likely to develop adverse events. In contrast, other factors including age ≤ 65 (AOR = 3.460; 95%CI: 1.511-7.922; P = 0.003), female gender (AOR = 2.362; 95%CI=1.089-5.124; P = 0.030), difficult cannulation (AOR = 4.527; 95%CI: 2.078-9.860; P < 0.001), and patients with cholangitis (AOR = 3.261; 95%CI: 1.204-8.832; P = 0.020) were strongly associated with a higher rate of post-ERCP pancreatitis. CONCLUSION: Advanced age has not been proved to be a risk factor for difficult cannulation, and secondary cannulation techniques can be safely and efficaciously utilized in this group. Patients with a Charlson Comorbidity Index ≥ 2 and difficult cannulation are associated with an increased overall adverse events rate, while age ≥ 80 years is not.

Prognostic and clinicopathological significance of SNHG20 in human cancers: a meta-analysis.

BACKGROUND: It has been widely reported that the expression levels of SNHG20 are elevated in diverse types of cancers, indicating that SNHG20 may participate in cancer initiation and development. Besides, accumulating evidence reveals that SNHG20 overexpression is also connected with poor clinical outcomes among cancer patients. Herein, we carry out a systematic meta-analysis to further determine the prognostic and clinical significance of SNHG20 expression in various human cancers. METHODS: Qualifying publications were selected by searching for keywords in PubMed, Embase, Web of Science and Cochrane Library databases, up to September 1, 2019. Pooled hazard ratio (HR) or odds ratio (OR) with corresponding 95% confidence interval (CI) was computed to estimate the strength of association between SNHG20 and survival of cancer patients or clinicopathology using Stata 14.0 software. RESULTS: In total, 15 studies encompassing 1187 patients met the inclusion criteria were ultimately enrolled for analysis. According to the meta-analysis, patients with high SNHG20 expression were markedly linked to poorer overall survival (OS) (pooled HR = 2.47, 95% CI 2.05-2.98, P = 0.000) and disease-free survival/recurrence-free survival/progression-free survival (DFS/RFS/PFS) (pooled HR = 2.37, 95% CI 1.60-3.51, P = 0.000). Additionally, regarding clinicopathology of patients, enhanced SNHG20 was correlated with advanced tumour-node-metastasis (TNM) stage (OR = 2.80, 95% CI 2.00-3.93, P = 0.000), larger tumor size (OR = 3.08, 95% CI 2.11-4.51, P = 0.000), positive lymph nodes metastasis (OR = 2.99, 95% CI 2.08-4.31, P = 0.000), higher tumor stage (OR = 4.51, 95% CI 2.17-9.37, P = 0.000) and worse histological grade (OR = 1.95, 95% CI 1.44-2.63, P = 0.000), but not with gender, smoking status or distant metastasis. CONCLUSIONS: Up-regulated SNHG20 expression is ubiquitous in different kinds of cancers. Moreover, up-regulated SNHG20 expression is capable of serving as an innovative predictive factor of inferior clinical outcomes in cancer patients. Nevertheless, higher-quality multicenter studies are required to corroborate our results.

Long noncoding RNA SNHG6 mainly functions as a competing endogenous RNA in human tumors.

Increased expression of the small nucleolar RNA host gene 6 (SNHG6) has been reported in different cancers, such as hepatocellular carcinoma, colorectal cancer, and lung cancer. The high expression level of SNHG6 is associated with tumor progression and poor prognosis. This paper provides an overview of recent studies on the oncogenic role and potential clinical utilities of SNHG6. Upregulated SNHG6 arrests tumor cell cycle and reduces apoptosis but promotes migration, invasion, metastasis, epithelial-mesenchymal transition (EMT), and chemoresistance in tumors. Mechanically, SNHG6 primarily sponges tumor suppressor microRNA (miRNA), functioning as a competing endogenous RNA. Once sponged, miRNA is unable to degrade, silence, or hamper the translation of its downstream, mostly oncogenic genes, ultimately driving cancer-related processes. Thus, SNHG6 might serve as a biomarker for cancer diagnosis and prognosis.

Prognostic value and therapeutic potential of the long noncoding RNA TP73-AS1 in cancers: A systematic review and meta-analysis.

Studies published in recent years have demonstrated that abnormal long noncoding RNA (lncRNA) antisense RNA to TP73 gene (TP73-AS1) expression is markedly associated with tumorigenesis, cancer progression and the prognosis of cancer patients. We aimed to explore the prognostic value of TP73-AS1 in multiple cancers. We comprehensively searched PubMed, Embase, Web of Science and the Cochrane Library (up to February 21, 2019). Hazard ratios (HRs), odds ratios (ORs) and the corresponding 95% confidence intervals (95% CIs) were calculated to estimate the association of TP73-AS1 with survival and clinicopathological features. The potential targets and pathways of TP73-AS1 in multiple cancers were summarized. Nineteen studies that involved thirteen types of cancers and 1329 cancer patients were identified as eligible for this meta-analysis. The results showed that high TP73-AS1 expression was significantly correlated with shorter overall survival (OS) (HR = 1.962, 95% CI 1.630-2.362) and disease-free survival (DFS) (HR = 2.050, 95% CI 1.293-3.249). The summary HRs of OS were 2.101 (95% CI 1.516-2.911) for gastric cancer (GC) and 1.920 (95% CI 1.253-2.942) for osteosarcoma. Subgroup analysis of OS demonstrated that the differential expression of TP73-AS1 in cancer tissues was a potential source of heterogeneity. Furthermore, increased TP73-AS1 expression was markedly associated with larger tumor size (OR = 2.759, 95% CI 1.759-4.330), advanced histological grade (OR = 2.394, 95% CI 1.231-4.656), lymph node metastasis (OR = 2.687, 95% CI 1.211-5.962), distant metastasis (OR = 4.145, 95% CI 2.252-7.629) and advanced TNM stage (OR = 2.633, 95% CI 1.507-4.601). The results of Egger's test and sensitivity analysis verified the robustness of the original results. High TP73-AS1 expression can predict poor survival and poor clinicopathological features in cancer patients and TP73-AS1 might be a potential biomarker and therapeutic target.

Association between Mediterranean diet adherence and colorectal cancer: a dose-response meta-analysis.

BACKGROUND: Mounting epidemiologic studies have investigated the potential inverse association between Mediterranean diet (MD) adherence and colorectal cancer (CRC) incidence and mortality. OBJECTIVES: This meta-analysis aimed to investigate the association between MD adherence and CRC incidence and mortality. METHODS: PubMed, Embase, and Web of Science were searched to identify eligible studies through September 2019. A random-effects model was used to estimate summary RRs and 95% CIs. RESULTS: This meta-analysis included 13 prospective cohort studies, of which 9 reported CRC incidence and 5 reported CRC mortality. The summary RR of CRC incidence was 0.90 (95% CI: 0.84, 0.96) for highest compared with lowest MD adherence and 0.96 (95% CI: 0.94, 0.99) per 2-score increase in MD adherence. The summary RRs for highest compared with lowest MD adherence were 0.82 for rectal cancer (95% CI: 0.71, 0.95), 0.94 for proximal colon cancer (95% CI: 0.87, 1.02), and 0.91 for distal colon cancer (95% CI: 0.79, 1.04). Neither the summary HR of overall mortality for highest compared with lowest pre- and postdiagnosis MD adherence, nor the summary HR of CRC-specific mortality for highest compared with lowest prediagnosis MD adherence achieved a value with statistical significance. CONCLUSIONS: Our meta-analysis supports the inverse association of MD adherence with CRC incidence, but not with overall mortality or CRC-specific mortality among those diagnosed with CRC.

Long noncoding RNA SNHG6 promotes proliferation and angiogenesis of cholangiocarcinoma cells through sponging miR-101-3p and activation of E2F8.

Cholangiocarcinoma (CCA) development is an extremely complex process with alterations occurring in numerous genes. SNHG6, a validated lncRNA, has been reported to regulate the expression of multiple tumor-related genes in hepatocellular carcinoma, colorectal cancer and breast cancer. Here, we elucidated the function and possible molecular mechanisms of SNHG6 in human CCA cells. Our results proved that the expression SNHG6 was upregulated in CCA tissues and cell lines. Ectopic expression of SNHG6 promoted cell proliferation, cell cycle progression, migration, and angiogenesis in CCA cells, whereas knockdown of SNHG6 repressed these cellular processes. Further mechanistic studies revealed that SNHG6 could compete with the transcription factor E2F8 to bind with miR-101-3p, thus affecting E2F8 expression. Taken together, these results provided a comprehensive analysis of the role of SNHG6 in CCA cells and offered important clues to understand the key roles of competing endogenous RNA (ceRNA) mechanisms in human cholangiocarcinoma.

Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects.

Quercetin is a kind of flavonoid compounds that comes from nature and is widely existed in the daily diet. Previous studies have found that quercetin has many effects such as anti-inflammatory, anti-oxidation and anti-cancer. Both in vivo and in vitro experiments have demonstrated that quercetin can exert anti-tumor effects by altering cell cycle progression, inhibiting cell proliferation, promoting apoptosis, inhibiting angiogenesis and metastasis progression, and affecting autophagy. This review summarizes the evidence for the pharmacological potential and inhibition of quercetin on cancers, supporting the viewpoint that quercetin should be adequately considered as a therapeutic agent against various cancers.

MicroRNA-195 as a prognostic factor for cancer survival outcome in China: a meta-analysis.

PURPOSE: MicroRNA-195 is dysregulated in different kinds of cancers and plays a pivotal role in tumorigenesis. It may function as a prognostic biomarker for cancers. However, the results from articles were not consistent. This study was designed to validate the prognostic value of microRNA-195 in human tumors. METHODS: We conducted a detailed search on PubMed until December 31, 2018. The quality of these publications was assessed on the basis of a list of key reviews presented by PRISMA statement. The pooled hazard ratios (HR) and pooled odds ratios (OR) of each 95% confidence interval (95% CI) were calculated to assess the effect. RESULTS: This meta-analysis included 12 studies involving 940 cancer patients to assess the prognostic value of miR-195 in different solid tumors. The results showed that patients with high expression of miR-195 had favorable tumor-node-metastasis (late vs early: pooled OR =0.16, 95% CI: 0.11-0.22, P<0.001), lymph node metastasis (pooled OR =0.25, 95% CI: 0.18-0.35, P<0.001) and distant metastasis (pooled OR =0.26, 95% CI: 0.13-0.52, P<0.001). At the same time, high levels of miR-195 expression were closely correlated with better overall survival (pooled HR =0.46, 95% CI: 0.36-0.58, P<0.001). CONCLUSION: Elevated microRNA-195 may serve as a potential biomarker to predict a favorable prognosis for various cancer types in China.

Comparison of esophageal stent placement versus endoscopic incision method for treatment of refractory esophageal anastomotic stricture.

BACKGROUND: Refractory esophageal anastomotic strictures are difficult to treat. Current treatments include esophageal stent placement (ESP) and the endoscopic incision method (EIM). This study was conducted to determine which treatment is better for patients with refractory esophageal anastomotic stricture. METHODS: This study retrospectively collected data of patients with refractory esophageal anastomotic stricture who underwent ESP or EIM between January 2012 and June 2018. Dysphagia scores before and after the procedure were recorded in both groups. The duration of relief during the follow-up period was recorded. RESULTS: Fifty patients were enrolled in this study, including 32 patients who underwent ESP and 18 who underwent EIM. Patients in the ESP group had a markedly larger diameter of dilatation than those in the EIM group (19.9±1.8 versus 11.0±1.9 mm, respectively; P0.001). However, the dysphagia score improved by 1.0±0.0 point in the ESP group and by 1.4±0.5 points in the EIM group (P<0.001). Nearly 70% of patients in the ESP group maintained lumen patency at 12 months. In contrast, only 50% of patients in the EIM group had persistent relief of stricture symptoms at 6 months and only 20% had relief at 12 months. Five patients had slight bleeding; none required blood transfusion. Thirteen patients in the ESP group had slight chest pain; seven of these required administration of a painkiller. CONCLUSIONS: EIM can rapidly relieve the symptoms of esophageal anastomotic stricture but ESP provides longer duration of relief. Both procedures are safe for patients with refractory esophageal anastomotic stricture.

Long noncoding RNA DANCR regulates proliferation and migration by epigenetically silencing FBP1 in tumorigenesis of cholangiocarcinoma.

Recently, long noncoding RNAs (lncRNAs) have been shown to play significant regulatory roles in human tumorigenesis. However, the biological function of lncRNAs in cholangiocarcinoma (CCA) remains largely unknown. In this study, DANCR was shown to be significantly upregulated in CCA. DANCR regulated the proliferation and migration of CCA cells in vitro. Moreover, downregulation of DANCR suppressed CCA cells proliferation in vivo. RNA-seq revealed that DANCR knockdown preferentially affected genes linked with cell proliferation and cell differentiation. Furthermore, mechanistic investigation validated that DANCR could bind EZH2 and modulate the histone methylation of promoter of FBP1, thereby regulating CCA cells growth and migration. Taken together, these results demonstrated the significant roles of DANCR in CCA and may provide a theoretical basis for clinical diagnosis and treatment of CCA.

Long noncoding RNAs as potential biomarkers and therapeutic targets in gallbladder cancer: a systematic review and meta-analysis.

BACKGROUND: Mounting evidence has shown that long noncoding RNAs (lncRNAs) can play a substantial role in gallbladder cancer (GBC) development as tumor promotors or suppressors, and their abnormal expression is relevant to GBC patient outcomes. We completed this systematic review and meta-analysis to explore the clinical significance and mechanisms of lncRNAs in GBC. METHODS: We conducted a comprehensive literature search and selected eligible records according to the inclusion and exclusion criteria. Hazard ratios (HRs) and odds ratios (ORs) were extracted or calculated to estimate the relationships of high lncRNA expression with GBC patient survival and clinical outcomes. RESULTS: Eighteen studies were identified as eligible for this systematic review and meta-analysis. Heterogeneity among HRs of overall survival (OS) was notably high (I2 = 86.2%, p < 0.001). Subgroup analysis suggested that overexpression of lncRNAs in a group that is upregulated in GBC showed a significant association with poor OS (HR = 2.454, 95% CI 2.004-3.004, I2 = 0%). Conversely, overexpression of lncRNAs in a downregulated group was markedly related to good OS (HR = 0.371, 95% CI 0.267-0.517, I2 = 0%). High expression levels of lncRNA AFAP1-AS1, MALAT1 and ROR were positively correlated with tumor size. Expression of lncRNA LET, LINC00152 and HEGBC exhibited a positive correlation with high T status. LncRNA LINC00152, HEGBC, MALAT1 and ROR showed a marked correlation with positive lymph node metastasis (LNM), while lncRNA GCASPC, MEG3, LET and UCA1 had the opposite effect. High expression levels of lncRNA HEGBC, PAGBC, PVT1 and UCA1 predicted high tumor node metastasis (TNM) stages, while lncRNA LET, GCASPC and MEG3 indicated low TNM stages. We also summarized the mechanisms of lncRNAs in GBC. CONCLUSION: Aberrant expression of several lncRNAs was indicative of the prognosis of GBC patients, and lncRNAs showed promise as biomarkers and therapeutic targets for GBC.

Clinical Significance of Prothrombin Time in Cholangiocarcinoma Patients with Surgeries.

Background: Prothrombin time (PT) can predict survival in several types of malignancies. This study aims to investigate the predictive values of PT levels in patients with cholangiocarcinoma (CCA). Methods: We retrospectively analyzed the PT from 86 CCA patients who underwent curative resection in our hospital from December 2008 to August 2017. The relationship between PT and survival times was analyzed through univariate and multivariate analyses (Cox proportional hazards model). Kaplan-Meier curves and log-rank test were used to assess the effects of PT on overall survival (OS) and tumor recurrence-free survival (RFS). Results: Increased PT level was an effective predictor for OS (P = 0.021; hazard ratio (HR), 1.799) and RFS (P = 0.016; HR, 1.871) in CCA patients, independent of age, tumor differentiation, and TNM stage. In the low PT level group (PT < 12.3 s), patients showed a higher mean OS (23.03 m vs. 14.38 m, P = 0.0250) and RFS (17.78 m vs. 8.30 m, P = 0.0511) than those with high PT levels (PT ≥ 12.3 s). A highly significant association was observed between high PT level and shortened OS (P = 0.0373) and worse RFS (P = 0.0151). Conclusion: Preoperative increase in PT can serve as a simple but effective predictor of poor survival in CCA patients who undergo curative surgeries.

Expression level and clinical significance of SNHG1 in human cancers: a meta-analysis.

Background: As reported by numerous research studies, the expression levels of SNHG1 (small nucleolar RNA host gene 1) are increased in different kinds of tumours, revealing that SNHG1 is likely to perform a crucial function in cancer prevalence and progression. Moreover, a mounting degree of evidence suggests that increased SNHG1 expression also has an association with poor medical outcomes among cancer patients. Materials and methods: Collection of qualifying research studies was performed through the retrieval of keywords in PubMed and Web of Science, up to March 20, 2018. This quantitative meta-analysis was carried out using Stata SE12.0 software and aimed at exploring the connection between the expression level of SNHG1 and clinicopathology. Results: Ten research studies, involving an aggregate of 715 patients, met the inclusion criteria. As suggested by the findings of the current meta-analysis, with regard to prognosis, the patients with high expression of SNHG1 had poorer overall survival (OS) (HR =3.36, 95% CI: 2.42, 4.67) and, with regard to their clinicopathology, increased SNHG1 was associated with advanced TNM stage (RR =1.88, 95% CI: 1.58, 2.24), poorly differentiated histological grade (RR =1.38, 95% CI:1.09, 1.76), and positive lymph node metastasis (RR =1.80, 95% CI: 1.42, 2.29). Conclusion: As revealed by this meta-analysis, elevated SNHG1 expression is typical in various types of cancer. In addition, elevated SNHG1 expression is likely to function as an advanced predictive element of poor prognosis and lymph node metastasis in various cancer types. Nonetheless, to date, it remains essential to carry out larger-size and better-designed research studies for the confirmation of our findings.

Long noncoding-RNA component of mitochondrial RNA processing endoribonuclease is involved in the progression of cholangiocarcinoma by regulating microRNA-217.

Cholangiocarcinoma (CCA) is a malignant tumor originating from bile duct epithelium and its incidence is increasing year by year. In recent years, long noncoding RNAs (lncRNAs) have been found to play an important role in the occurrence and progression of malignant tumors. In the present study, for the first time, abnormal expression of lnc-RNA component of mitochondrial RNA processing endoribonuclease (RMRP) and its possible role in CCA were found. We explored the effects of RMRP on various behaviors of CCA cells in vitro and in vivo. In addition, by second-generation sequencing, we explored the microRNA expression profiles that RMRP may affect in the HCCC-9810 cell line. We also validated and explored the role of microRNA-217 (miR-217) with high differential expression by in vitro experiments. Our findings indicated that RMRP can play a part in promoting cancer by regulating the expression of miR-217. RMRP is involved in the progression of CCA and can be a novel indicator of poor prognosis in patients with CCA.

SP/NK-1R promotes gallbladder cancer cell proliferation and migration.

Aberrant substance P/neurokinin-1 receptor (SP/NK-1R) system activation plays a critical role in various disorders, however, little is known about the expression and the detailed molecular mechanism of the SP and NK-1R in gallbladder cancer (GBC). In this study, we firstly analyzed the expression and clinical significance of them in patients with GBC. Then, cellular assays were performed to clarify their biological role in GBC cells. Moreover, we investigated the molecular mechanisms regulated by SP/NK-1R. Meanwhile, mice xenografted with human GBC cells were analyzed regarding the effects of SP/NK1R complex in vivo. Finally, patient samples were utilized to investigate the effect of SP/NK-1R. The results showed that SP and NK-1R were highly expressed in GBC. We found that SP strongly induced GBC cell proliferation, clone formation, migration and invasion, whereas antagonizing NK-1R resulted in the opposite effects. Moreover, SP significantly enhanced the expression of NF-κB p65 and the tumor-associated cytokines, while, Akt inhibitor could reverse these effects. Further studies indicated that decreasing activation of NF-κB or Akt diminished GBC cell proliferation and migration. In consistent with results, immunohistochemical staining showed high levels of Akt, NF-κB and cytokines in tumor tissues. Most importantly, the similar conclusion was obtained in xenograft mouse model. Our findings demonstrate that NK-1R, after binding with the endogenous agonist SP, could induce GBC cell migration and spreading via modulation of Akt/NF-κB pathway.

Pivotal prognostic and diagnostic role of the long non­coding RNA colon cancer­associated transcript 1 expression in human cancer (Review).

Long non­coding RNAs (lncRNAs) have been classically defined as regulatory RNA members >200 nucleotides in length, without detectable open­reading frames to encode proteins. Previous studies have demonstrated that lncRNAs serve critical roles in multiple cancer types. Colon cancer­associated transcript 1 (CCAT1), a novel cancer­associated lncRNA, is significantly overexpressed in a number of malignancies. Functionally, as an oncogenic lncRNA, CCAT1 is involved in proliferation, migration, cell cycle progression, apoptosis, chemoresistance and other biological processes of cancer cells through complex regulation mechanisms in the cytoplasm or nucleus. In clinical applications, CCAT1 is additionally positively associated with histological differentiation, tumour node metastasis stage, vascular invasion, overall survival and recurrence­free survival, which demonstrates its important role as a diagnostic and prognostic marker in cancer. The present review summarises the current research progress of the oncogenic potential and clinical uses of CCAT1 in various human cancer types.