CCDC25 suppresses clear cell renal cell carcinoma progression by LATS1/YAP-mediated regulation of the hippo pathway.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent renal cancers, and the molecular mechanisms underlying its progression are still not fully understood. The expression of CCDC25, a notably underexpressed gene in many tumors, has been understudied in ccRCC. This research aims to explore the role of CCDC25 in ccRCC's clinical outcomes and uncover the molecular pathways influenced by it. METHODS: A multi-tiered approach was adopted involving bioinformatic analysis, tissue sample evaluation, in vitro and in vivo experiments. CCDC25 expression levels in tumor vs. normal tissues were quantified using Western blot and immunofluorescence studies. Cell proliferation and migration were analyzed using CCK8, EDU, Transwell assays, and wound healing assays. RNA sequencing was performed to elucidate the molecular pathways affected, followed by detailed protein-protein interaction studies and mouse xenograft models. RESULTS: CCDC25 was predominantly underexpressed in ccRCC tumors and associated with advanced clinical stages and poor prognosis. Overexpression of CCDC25 in renal cancer cell lines resulted in reduced proliferation and migration. RNA sequencing revealed significant alterations in the Hippo pathway. Overexpression of CCDC25 inhibited the expression of downstream Hippo pathway proteins ITGA3 and CCND1 and promoted YAP phosphorylation. Mechanistic studies showed that CCDC25 interacts with YAP and influences YAP phosphorylation through LATS1. In vivo, CCDC25 overexpression inhibited tumor growth and promoted apoptosis. CONCLUSION: CCDC25 acts as a potential tumor suppressor in ccRCC by inhibiting cell proliferation and migration, potentially through regulating the Hippo signaling pathway. These findings highlight the potential of CCDC25 as a therapeutic target in ccRCC treatment.

PCMT1 is a potential target related to tumor progression and immune infiltration in liver cancer.

BACKGROUND: Liver cancer is a prevalent and deadly form of cancer with high incidence and mortality rates. The PCMT1 protein has been linked to cell anti-apoptosis and tumor metastasis, but its significance in liver hepatocellular carcinoma (LIHC) remains largely unexplored. METHODS: We conducted a pan-cancer analysis to examine the expression differences of PCMT1. Kaplan-Meier curves were employed to assess the prognostic impact of PCMT1 on LIHC patients, and we investigated the association between PCMT1 and clinical features, which we validated using a GEO therapeutic dataset. Gene enrichment analysis helped identify signaling pathways associated with PCMT1 expression. Moreover, we evaluated the relationship between PCMT1 and immune cell infiltration, as well as the differences in gene mutations between high-expression and low-expression groups. In vitro and in vivo experiments were performed to assess the effect of PCMT1 on tumor cell lines and mouse tumor models, and potential pathways were explored through gene sequencing. RESULT: PCMT1 is highly expressed in most tumors and exhibits a significant association with prognosis in LIHC patients. Pathway enrichment analysis revealed that PCMT1 is involved in cell cycle regulation, immunity, and other processes. Further immune analysis demonstrated that high expression of PCMT1 could reduce tumor-killing immune cell infiltration. In vitro experiments indicated that PCMT1 knockdown could inhibit cancer cell proliferation and migration while promoting apoptosis. In vivo experiments showed that PCMT1 knockdown significantly reduced tumor growth rate, enhanced CD8+T cell infiltration, and increased caspase-3 expression in the tumor area. Gene sequencing suggested that PCMT1 may function through the PI3K-AKT pathway. CONCLUSION: Our findings suggest that PCMT1 acts as a promoter of liver cancer progression and may serve as a novel prognostic indicator and therapeutic target for patients with LIHC.

Intergenic CircRNA Circ_0007379 Inhibits Colorectal Cancer Progression by Modulating miR-320a Biogenesis in a KSRP-Dependent Manner.

Circular RNAs (circRNAs) are covalently closed RNA structures that play multiple roles in tumorigenesis and progression. Compared with exon‒intron circRNAs, the biological functions and implications of intergenic circRNAs in human cancer are still poorly understood. Here, we performed circRNA microarray analysis and identified an intergenic circRNA, circ_0007379, that was significantly downregulated in patients with colorectal cancer (CRC). The biogenesis of circ_0007379 was mediated by reverse complementary matches (RCMs) and was negatively regulated by the RNA helicase DHX9. Functionally, circ_0007379 suppressed CRC cell growth and metastasis in cell culture as well as in patient-derived organoid and xenograft models. Mechanistically, circ_0007379 acted as a scaffold to facilitate the processing of both pri-miR-320a and pre-miR-320a in a KSRP-dependent manner, leading to miR-320a maturation and subsequent repression of transcription factor RUNX1 expression. Thus, our findings establish a previously unrecognized function of circRNA in inhibiting CRC progression.

Clinicopathological and prognostic significance of LKB1 expression in gastric cancer: a systematic review and meta-analysis.

Many studies report Liver kinase B1 (LKB1) plays a critical role in gastric cancer (GC). However, the relationship between LKB1 and the clinicopathological parameters of GC patients remains controversial. This meta-analysis aimed to investigate the above question and re-evaluate the prognostic significance of LKB1 in GC patients. We searched PubMed, Web of Science, Cochrane Library, Google Scholar, CNKI, and Wan Fang to identify relevant studies published before April 20, 2023. After careful screening, 11 studies involving 1767 patients were included. We found that LKB1 expression was significantly related to tumor size (OR 0.515; 95% CI 0.316-0.839; P < 0.01), differentiation (OR 0.643; 95% CI 0.521-0.794; P < 0.001), depth of invasion (OR 0.397; 95% CI 0.319-0.494; P < 0.001), lymph node metastasis (OR 0.487; 95% CI 0.397-0.598; P = 0.01), and TNM stage (OR 0.362; 95% CI 0.293-0.447; P = 0.006). However, LKB1 was unrelated to gender and age (P > 0.05). Moreover, low LKB1 expression was significant correlate with overall survival (OS) (HR = 1.59; 95% CI 1.29-1.96; P < 0.001). In conclusion, LKB1 expression is related to tumor size, differentiation, depth of invasion, lymph node metastasis, and TNM stage, and low LKB1 expression can predict a poor prognosis. LKB1 is a potentially valuable prognosis signature and therapeutic target in GC patients.

Encoding gene RAB3B exists in linear chromosomal and circular extrachromosomal DNA and contributes to cisplatin resistance of hypopharyngeal squamous cell carcinoma via inducing autophagy.

Cisplatin (DDP) resistance is an important factor that decreases the effect of chemotherapy, thus leading to local recurrence and lymph node metastasis of hypopharyngeal squamous cell carcinoma (HSCC). We aimed to explore the role and mechanism of extrachromosomal circular DNA (eccDNA) in the DDP resistance of HSCC. In our research, the HSCC cell line FaDu and the DDP-resistant cell line FaDu/DDP were used as subjects. eccDNA sequencing and whole transcriptome sequencing were conducted, followed by a combined analysis of the two sequencing profiles. Outward PCR, inward PCR and Sanger sequencing were used to verify sequences of the eccDNAs. Bioinformatics analysis based on TCGA/GEO was performed in addition to plasmid transfection, RNA interference, qRT-PCR and Western blot experiments to verify the expression level of RAB3B amplified from eccDNA. mRFP-GFP-LC3 adenoviral particle transfection and transmission electron microscopy were used to detect autophagic flux. Finally, we evaluated the role of RAB3B in FaDu/DDP cells and patient-derived organoids. Our results showed that we purified and sequenced more than 10 thousand eccDNAs from the two cell lines, and the size of the eccDNAs was distributed from 0.01 kb to 1000 kb. The combined analysis between eccDNA and transcript sequencing indicated that there were some highly expressed genes that were completely or partially transcribed from related sequences of eccDNAs and not from genome linear DNA. We further screened and verified the encoding gene RAB3B using full-length sequences that might be amplified from eccDNA [chr1circle 46219-52682 kb]. Finally, we confirmed that RAB3B could promote DDP resistance in HSCC by inducing autophagy. The eccDNA might play significant roles in DDP resistance in HSCC by amplifying related functional genes. Further study is needed to explore the novel mechanisms of eccDNA in the drug resistance of HSCC.

Applicability of TIVAP versus PICC in non-hematological malignancies patients: A meta-analysis and systematic review.

BACKGROUND: Applicability of totally implantable venous access port (TIVAP) and peripherally inserted central venous catheter (PICC) in non-hematological malignancies patients remains controversial. METHODS: A systematic studies search in the public databases PubMed, EMBASE, Wan Fang, CNKI (China National Knowledge Infrastructure), the Cochrane Library and Google Scholar (updated to May 1, 2020) was performed to identify eligible researches. All statistical tests in this meta-analysis were performed using Stata 12.0 software (Stata Corp, College Station, TX). A P value less than 0.05 was considered statistically significant. RESULTS: Thirteen studies were included in this final meta-analysis. The pooled data showed that compared with PICC, TIVAP was associated with a higher first-puncture success rate (OR:2.028, 95%CI:1.25-3.289, P<0.05), a lower accidental removal rate (OR:0.447, 95%CI:0.225-0.889, P<0.05) and lower complication rates, including infection (OR:0.570, 95%CI: 0.383-0.850, P<0.05), occlusion (OR:0.172, 95%CI:0.092-0.324, P<0.05), malposition (OR:0.279, 95%CI:0.128-0.608, P<0.05), thrombosis (OR:0.191, 95%CI, 0.111-0.329, P<0.05), phlebitis (OR:0.102, 95%CI, 0.038-0.273, P<0.05), allergy (OR:0.155, 95%CI:0.035-0.696, P<0.05). However, no difference was found in catheter life span (P>0.05) and extravasation (P>0.05). Moreover, TIVAP is more expensive compared with PICC in six-month use (weighted mean difference:3.132, 95%CI:2.434-3.83, P<0.05), but is much similar in 12 months use (P>0.05). CONCLUSION: For the patients with non-hematological malignancies, TIVAP was superior to PICC in the data related to placement and the incidence of complications. Meanwhile, TIVAP is more expensive compared with PICC in six-month use, but it is much similar in twelve-month use.

The protective effects of salvianolic acid A against hepatic ischemia-reperfusion injury via inhibiting expression of toll-like receptor 4 in rats.

INTRODUCTION: Ischemia-reperfusion injury (IRI) is a serious complication of hepatectomy and liver transplantation. The aim of this study was to evaluate the protective effects of salvianolic acid-A (Sal-A) against IRI-induced hepatocellular injury. MATERIAL AND METHODS: Forty rats were randomly divided into the following four groups: (1) sham group, (2) IR group, (3) Sal-A(10) group and (4) Sal-A(20) group. After 90 min of ischemia and 6 h of reperfusion, serum alanine aminotransferease (ALT) and apartate aminotransferase (AST) levels were measured; the amounts of malondialdehyde (MDA) and superoxide dismutase (SOD) in the liver tissue were determined; the expression of Bcl-2 and caspase-3 was detected and the severity of apoptosis, inflammation and pathological alterations were evaluated. Also apoptosis and mRNA and protein levels of TLR4 (toll-like receptor 4) were tested. RESULTS: The serum aminotransferases, hepatic MDA concentration, and apoptotic cells in the IR group were significantly higher than in the sham group (p < 0.01), whereas the Sal-A group values were lower than in the IR group (p < 0.05). Compared with the IR group, the Sal-A groups had significantly higher Bcl-2 expression and downregulated cleaved caspase-3 expression in liver tissue. Moreover, increased mRNA and protein levels of TLR4 in IR rats and Sal-A could improve the increased mRNA and protein levels of TLR4. CONCLUSIONS: Sal-A had a synergistically protective effect on the liver tissue against IRI that might be due to decreased oxidative stress, inflammation, hepatocellular apoptosis and include, at least in part, the regulation of TLR4.

The transcription factor FoxM1 activates Nurr1 to promote intestinal regeneration after ischemia/reperfusion injury.

FoxM1 is involved in the regeneration of several organs after injury and expressed in the intestinal mucosa. The intrinsic mechanism of FoxM1 activity in the mucosa after intestinal ischemia/reperfusion (I/R) injury has not been reported. Therefore, we investigated the role of FoxM1 in mediating intestinal mucosa regeneration after I/R injury. Expression of FoxM1 and the proliferation of intestinal mucosa epithelial cells were examined in rats with intestinal I/R injury and an IEC-6 cell hypoxia/reperfusion (H/R) model. The effects of FoxM1 inhibition or activation on intestinal epithelial cell proliferation were measured. FoxM1 expression was consistent with the proliferation of intestinal epithelial cells in the intestinal mucosa after I/R injury. Inhibition of FoxM1 expression led to the downregulation of Ki-67 expression mediated by the inhibited expression of Nurr1, and FoxM1 overexpression promoted IEC-6 cell proliferation after H/R injury through activating Nurr1 expression. Furthermore, FoxM1 directly promoted the transcription of Nurr1 by directly binding the promoter of Nurr1. Further investigation showed low expression levels of FoxM1, Nurr1, and Ki-67 in the intestinal epithelium of patients with intestinal ischemic injury. FoxM1 acts as a critical regulator of intestinal regeneration after I/R injury by directly promoting the transcription of Nurr1. The FoxM1/Nurr1 signaling pathway represents a promising therapeutic target for intestinal I/R injury and related clinical diseases.

Clinicopathological and prognostic significance of the RUNX3 expression in gastric cancer: a systematic review and meta-analysis.

BACKGROUND: The relationship between expression of runt related transcription factor 3 (RUNX3) and clinicopathological parameters of the patients with gastric cancer (GC) is controversial. METHODS: The studies were retrieved from those already published essay in PubMed, EMBASE, Wan Fang, CNKI (China National Knowledge Infrastructure), the Cochrane Library and Google Scholar. All statistical tests in this meta-analysis were performed using Stata 10.0 software (Stata Corp, College Station, TX). A P value less than 0.05 was considered statistically significant. RESULTS: A total of nine studies involving 796 patients were included in final meta-analysis. The pooled data showed that expression of RUNX3 was significant correlated with tumor's differentiation (OR = 0.387; 95%CI: 0.237-0.633; P = 0.000), depth of invasion (OR = 0.443; 95%CI: 0.273-0.717; P = 0.001), lymph node metastasis (OR = 0.394; 95%CI: 0.259-0.598; P = 0.000), distant metastasis (OR = 0.403; 95%CI: 0.213-0.764; P = 0.005) and TNM stage (OR = 0.461; 95%CI, 0.322-0.659; P = 0.000) in GC. Expression of RUNX3 was significant correlated with good overall survival (OS) [1-year OS (OR = 2.735; 95%CI: 1.966-3.806; P = 0.000), 3-year OS (OR = 4.782; 95%CI: 3.634-6.292; P = 0.000), 5-year OS (OR = 5.191; 95%CI: 3.775-7.138; P = 0.000]. However, RUNX3 was not correlated with gender (OR = 1.409; 95%CI: 0.986-2.014; P = 0.060). CONCLUSION: RUNX3 expression correlates with tumor's differentiation, depth of invasion, lymph node metastasis, distant metastasis, TNM stage and OS of GC patients.

Clinicopathological and prognostic significance of FoxM1 in gastric cancer: A meta-analysis.

BACKGROUND: The relationship between expression of FoxM1 and clinical parameters of patients with gastric cancer (GC) has yet to be fully established. METHODS: A systematic search was performed. Odds ratio (OR) and confidence interval (CI) were used to assess association between expression of FoxM1 and clinical parameters and the prognostic value of patients with GC. RESULTS: Eight studies involving 529 patients with GC were identified. Overall, the pooled results showed that expression of FoxM1 was associated with TNM stage (OR: 0.482, 95%CI: 0.275-0.845, P = 0.011), depth of invasion (OR: 0.617, 95%CI: 0.382-0.998, P = 0.049) and lymph node metastasis (OR: 2.084, 95%CI: 1.305-3.328, P = 0.002) in the patients with GC. Whereas, expression of FoxM1 was not associated with gender (OR: 1.143, 95%CI: 0.726-1.799, P = 0.564) and tumors' differentiation (OR: 0.991, 95%CI: 0.624-1.575, P = 0.971) of GC. Expression of FoxM1 was also associated with poor prognosis of overall survival (OS) in the patients with GC (one year OS: OR: 0.218, 95%CI: 0.103-0.459, P = 0.000; three years OS: OR: 0.178, 95%CI: 0.093-0.340, P = 0.000; five years OS: OR: 0.180, 95%CI: 0.095-0.341, P = 0.000). CONCLUSION: Expression of FoxM1 is associated with TNM stage, depth of invasion, lymph node metastasis and poor prognosis of the patients with GC.

Prognostic and clinical significance of claudin-1 in colorectal cancer: A systemic review and meta-analysis.

BACKGROUND: The current reports on the association of claudin-1 expression with colorectal cancer (CRC) result were controversial. Thus, we conducted a meta-analysis to assess the correlation between claudin-1 expression and the clinical parameters and assess the prognostic value of claudin-1 in CRC. METHODS: Systematic searches on PubMed, Embase, Elsevier, CNKI (China National Knowledge Infrastructure), Wanfang data and Cochrane Library prior to August 2016 were performed. The pooled odds ratio (OR) with its 95% confidence interval (95 %CI) was used to assess association between claudin-1 expression and clinical parameters of CRC patients, and to assess association between claudin-1 expression and the prognostic value of CRC patients. RESULTS: Eight studies with a total of 1146 CRC patients were included. Overall, the pooled results showed that low expression of claudin-1 was associated with TNM III-IV stage of CRC patients (OR: 1.714, 95%CI: 1.215-2.418, P = 0.002). Low expression of claudin-1 was also associated with a poor survival in CRC patients (one year survival rate: OR: 2.112, 95%CI: 1.028-4.339, P = 0.042; three years survival rate: OR: 1.501, 95%CI: 1.030-2.186, P = 0.035; five years survival rate: OR: 1.794, 95%CI: 1.139-2.439, P = 0.000). Whereas, low expression of claudin-1 is not associated with gender (OR: 1.259, 95%CI: 0.957-1.657, P = 0.100), tumors' differentiation (OR: 1.317, 95%CI: 0.916-1.892, P = 0.137), depth of invasion (OR: 1.016, 95 %CI: 0.701-1.472, P = 0.935) and lymph node metastasis group (OR: 1.286, 95% CI: 0.982-1.684, P = 0.06) of CRC. CONCLUSIONS: Low expression of claudin-1 is associated with TNM III-IV stage and poor prognosis of CRC patients. Low expression of claudin-1 is not associated with gender, tumors' differentiation depth of invasion and lymph node involvement of CRC patients.

Generation of cylindrically symmetric modes and orbital-angular-momentum modes with tilted optical gratings inscribed in high-numerical-aperture fibers.

Optical fiber with high numerical aperture (NA) can efficiently relieve the degeneracy of higher-order linearly polarized modes. The degeneracy relief is investigated in two types of high-NA fibers, i.e., low-index-cladding fiber and high-index-core fiber. A naked-core fiber, as with low-index cladding, can be used theoretically to generate the orbital-angular-momentum mode (OAMM) HE21 and the cylindrically symmetric modes (CSMs) TM01 and TE01. A high-index-core fiber incorporated with high-contrast-index structure can be used similarly to obtain OAMM HE31. The generation of both CSMs and OAMMs required tilted optical gratings to couple the fundamental core mode HE11 into these modes. The tilt angle and modulation period of the grating fringes can be calculated simply and visually with the method proposed in this article.