LncRNA LINC01537 Promotes Gastric Cancer Metastasis and Tumorigenesis by Stabilizing RIPK4 to Activate NF-κB Signaling.

Many studies reported that long noncoding RNAs (lncRNAs) play a critical role in gastric cancer (GC) metastasis and tumorigenesis. However, the underlying mechanisms of lncRNAs in GC remain unexplored to a great extent. LINC01537 expression level was detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). Its biological roles in GC were then investigated using functional experiments. In order to investigate the underlying mechanism of LINC01537 in GC, RNA pull-down, RNA immunoprecipitation, and ubiquitination assays were performed. LINC01537 was significantly overexpressed in GC tissues and associated with a poor prognosis. Functional experimental results revealed that LINC01537 promoted the proliferation, invasion, and migration of GC cells. The animal experiments revealed that LINC01537 promoted tumorigenesis and metastasis in vivo. Mechanistically, LINC01537 stabilizes RIPK4 by reducing the binding of RIPK4 to TRIM25 and reducing its ubiquitination degradation, thereby promoting the expression of the NF-κB signaling pathway. According to our findings, the LINC01537-RIPK4-NF-κB axis promoted GC metastasis and tumorigenesis.

A novel prognostic signature based on cuproptosis-related lncRNA mining in colorectal cancer.

Background: Colorectal cancer (CRC) is a common malignant tumor that affects the large bowel or the rectum. Cuproptosis, recently discovered programmed cell death process, may play an important role in CRC tumorigenesis. Long non-coding RNAs (lncRNAs) can alter the proliferation of colorectal cancer cells through the control and activation of gene expression. To date, cuproptosis-related lncRNAs, have not been investigated as potential predictive biomarkers in colorectal cancer. Methods: The mRNA and lncRNA expression data of colorectal cancer were gathered from The Tumor Genome Atlas (TCGA) database, and Pearson correlation analysis and univariate Cox regression analysis were used to identify the lncRNAs with differential prognosis. Colorectal cancer was classified using consistent clustering, and the clinical significance of different types, tumor heterogeneity, and immune microenvironment differences was investigated. The differential lncRNAs were further screened using LASSO regression to develop a risk scoring model, which was then paired with clinicopathological variables to create a nomogram. Finally, the copy number changes in the high-risk and low-risk groups were compared. Results: Two clusters were formed based on the 28 prognostic cuproptosis-related lncRNAs, and the prognosis of cluster 2 was found to be significantly lower than that of cluster 1. Cluster 1 showed increased immune cell infiltration and immunological score, as well as strong enrichment of immune checkpoint genes. Next, LASSO regression was used to select 11 distinctive lncRNAs, and a risk score model was constructed using the training set to distinguish between high and low-risk groups. Patients in the high-risk group had a lower survival rate than those in the low-risk group, and both the test set and the total set produced consistent results. The AUC value of the ROC curve revealed the scoring model's efficacy in predicting long-term OS in patients. Moreover, the model could be used as an independent predictor when combined with a multivariate analysis of clinicopathological features, and our nomogram could be used intuitively to predict prognosis. Conclusion: Collectively, we developed a risk model using 11 differential lncRNAs and demonstrated that the model has predictive value as well as clinical and therapeutic implications for predicting prognosis in CRC patients.

Three-dimensional versus two-dimensional laparoscopic surgery for rectal cancer: better promote postoperative sexual and urinary function of a propensity-matched study.

Laparoscopic total mesorectal excision (TME) with autonomic nerve preservation (ANP) is a common procedure for rectal cancer (RC), associated with a high prevalence of postoperative urogenital and anorectal dysfunctions. Compared to 2D laparoscopy, 3D laparoscopy provides better depth perception of the surgical field and hand-eye coordination to achieve better outcomes. We compared the performance of 2D and 3D laparoscopy on preserving urogenital and anorectal function in TME+ANP surgery for rectal cancer using propensity-score matching. Data were collected from consecutive male patients who underwent 3D or 2D laparoscopic TME+ANP for primary RC at our institution between March 2012 and December 2020. The primary outcome was sexual and urinary function 1 year after surgery. A total of 450 male patients were eligible. After 1:1 matching, 146 cases were included in each group for analysis. One year after surgery, the prevalence of sexual dysfunction (International Index of Erectile Function score <26) was 8.22% in the 3D laparoscopic group and 44.52% in the 2D laparoscopic group, respectively (P=0.000) and a significant difference in the incidence of urinary retention was observed (n=3 and 24, respectively (P=0.000)). Moreover, blood loss, operative time, duration of hospital stay, and the time to first flatus in the 3D laparoscopic group were significantly less than in the 2D laparoscopic group. In conclusion, 3D laparoscopic TME is associated with lower incidences of postoperative sexual and urinary dysfunction than 2D laparoscopic TME for rectal cancer in male patients.

Long noncoding RNA OVAAL enhances nucleotide synthesis through pyruvate carboxylase to promote 5-fluorouracil resistance in gastric cancer.

5-Fluorouracil (5-FU) is widely used in gastric cancer treatment, yet 5-FU resistance remains an important clinical challenge. We established a model based on five long noncoding RNAs (lncRNA) to effectively assess the prognosis of gastric cancer patients; among them, lncRNA OVAAL was markedly upregulated in gastric cancer and associated with poor prognosis and 5-FU resistance. In vitro and in vivo assays confirmed that OVAAL promoted proliferation and 5-FU resistance of gastric cancer cells. Mechanistically, OVAAL bound with pyruvate carboxylase (PC) and stabilized PC from HSC70/CHIP-mediated ubiquitination and degradation. OVAAL knockdown reduced intracellular levels of oxaloacetate and aspartate, and the subsequent pyrimidine synthesis, which could be rescued by PC overexpression. Moreover, OVAAL knockdown increased sensitivity to 5-FU treatment, which could be reversed by PC overexpression or repletion of oxaloacetate, aspartate, or uridine. OVAAL overexpression enhanced pyrimidine synthesis to promote proliferation and 5-FU resistance of gastric cancer cells, which could be abolished by PC knockdown. Thus, OVAAL promoted gastric cancer cell proliferation and induced 5-FU resistance by enhancing pyrimidine biosynthesis to antagonize 5-FU induced thymidylate synthase dysfunction. Targeting OVAAL-mediated nucleotide metabolic reprograming would be a promising strategy to overcome chemoresistance in gastric cancer.

Magnetic resonance neuroimaging promotes the preservation of pelvic autonomic nerves in laparoscopic total mesorectal excision: a comparative study.

BACKGROUND: How to preserve pelvic autonomic nerves system (PANS) in total mesorectal excision (TME) is still a technical challenge for gastrointestinal surgeons, and nerve preservation according to preoperative magnetic resonance imaging (MRI) is a hot topic in pelvic surgery. The purpose of this study was to assess the postoperative urogenital function of patients with rectal cancer (RC) who underwent preoperative and postoperative neuroimaging of PANS vs. patients who did not. METHODS: Patients meeting the inclusion criteria were prospectively enrolled in a magnetic resonance neuroimaging (MRN) group from June 2018, while primary RC patients from January 2016 to May 2018 who met the inclusion criteria were enrolled in a non-MRN group. Patients in the MRN group underwent MRN examination before operation and 6 months after operation, while those in the non-MRN group were collected and analyzed retrospectively. RESULTS: Based on International Prostate Symptom Score (IPSS) and International Index of Erectile Function 5 (IIEF5) scores at 6 months, the postoperative urinary and sexual function of male patients in the MRN group were significantly better than that in the non-MRN group (P<0.05). In addition, based on International Consultation on Incontinence modular Questionnaire on Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) and Female Sexual Function Index (FSFI) scores at 6 months, the postoperative sexual function of female patients in the MRN group was significantly better than that in the non-MRN group (P<0.05). CONCLUSIONS: In the present study, we constructed a three-dimensional (3D) presentation of PANS based on preoperative MRN which showed in vivo pelvic autonomous innervation. This may promote the preservation of PANS during TME and reduce the postoperative urogenital dysfunction rate.

Long Non-Coding RNA STARD13-AS Suppresses Cell Proliferation And Metastasis In Colorectal Cancer.

BACKGROUND: Dysregulation of long non-coding RNAs (lncRNAs) is closely related with the progression of cancer in humans. The functional and regulatory roles of lncRNAs in colorectal cancer (CRC) are still largely unclear. The purpose of this study is to explore the function of lncRNA STARD13-AS in CRC. METHODS: The bioinformatics tool "GEPIA" was used to predict the potential expression of STARD13-AS in CRC. qRT-PCR was used to evaluate the relative expression level of STARD13-AS in CRC cells lines and tissues samples. The functional involvement of STARD13-AS in the CRC cells was assessed using MTT assay, flow cytometry, and Transwell assay. The expression levels of cyclin D, cyclin E, E-cadherin, N-cadherin, and vimentin were assessed using Western blot. RESULTS: Bioinformatics prediction and qRT-PCR results showed that STARD13-AS expression was decreased in CRC tissues. Patients with low STARD13-AS expression exhibited distant and lymphatic metastasis as well as enhancement in tumor size. STARD13-AS expression was downregulated in CRC cell lines compared to normal human colon mucosal epithelial cell line NCM460 and STARD13-AS expression in SW620 and LoVo cell lines was lowest. Moreover, we observed that while STARD13-AS overexpression suppressed the cell cycle, proliferation, migration, and invasion, while promoted apoptosis both in LoVo and SW620 cells. In addition, STARD13-AS overexpression inhibited Cyclin E, Cyclin D, N-cadherin and vimentin expression, and promoted E-cadherin expression both in LoVo and SW620 cells. CONCLUSION: Expression of STARD13-AS suppresses cell proliferation and metastasis in CRC, suggesting that STARD13-AS might act as a potential target for CRC treatment.

Small metal soft tissue foreign body extraction by using 3D CT guidance: a reliable method.

OBJECTIVE: To introduce a useful and accurate technique for the locating and removal of small metal foreign bodies in the soft tissues. METHODS: Eight patients presented with suspected small metal foreign bodies retained in the soft tissues of various body districts. Under local anesthesia, 3-6 pieces of 5 ml syringe needles or 1 ml syringe needles were induced through three different planes around the entry point of the foreign bodies. Using these finders, the small metal FBs were confirmed under 3D CT guidance. Based on the CT findings, the soft tissues were dissected along the path of the closest needle and the FBs were easily found and removed according to the relation with the closest needle finder. RESULTS: Eight metal foreign bodies (3 slices, 3 nails, 1 fish hook, 1 needlepoint) were successfully removed under 3D CT guidance in all patients. The procedures took between 35 min and 50 min and the operation times took between 15 min and 25 min. No complications arose after the treatment. CONCLUSION: 3D CT-guided technique is a good alternative for the removal of small metal foreign body retained in the soft tissues as it is relatively accurate, reliable, quick, carries a low risk of complications and can be a first-choice procedure for the extraction of small metal foreign body.