Peptide encoded by lncRNA BVES-AS1 promotes cell viability, migration, and invasion in colorectal cancer cells via the SRC/mTOR signaling pathway.

Long non-coding RNAs (lncRNAs) have been revealed to harbor open reading frames (ORFs) that can be translated into small peptides. The peptides may participate in the pathogenesis of colorectal cancer (CRC). Herein, we investigated the role of a lncRNA BVES-AS1-encoded peptide in colorectal tumorigenesis. Through bioinformatic analysis, lncRNA BVES-AS1 was predicted to have encoding potential and to be associated with poor prognosis of patients with CRC. In CRC cells, BVES-AS1 was validated to encode a 50-aa-length micro-peptide, named BVES-AS1-201-50aa, through a western blotting method. BVES-AS1-201-50aa enhanced cell viability and promoted the migratory and invasive capacities of HCT116 and SW480 CRC cells in vitro, validated via CCK-8 assay and transwell assay, respectively. Immunofluorescence assay showed that BVES-AS1-201-50aa increased the expression of proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase 9 (MMP9) in CRC cells. We further verified that BVES-AS1-201-50aa targeted and activated the Src/mTOR signaling pathway in CRC cells by co-immunoprecipitation (Co-IP) experiment, qualitative proteomic analysis, and western blotting. Our findings demonstrated that BVES-AS1 could encode a micro-peptide, which promoted CRC cell viability, migration, and invasion in vitro. Our current work broadens the diversity and breadth of lncRNAs in human carcinogenesis.

The long non-coding RNA LIMT inhibits metastasis of hepatocellular carcinoma and is suppressed by EGF signaling.

BACKGROUND: The long non-coding RNA LIMT (lncRNA inhibiting metastasis) acts as a tumor suppressor factor in some cancers. However, the biological role of LIMT in hepatocellular carcinoma (HCC) has not been explored. METHODS AND RESULTS: Quantitative real-time PCR was performed to evaluate the expression of LIMT in HCC tissue. The effects of LIMT on tumor growth and metastasis were assessed by in vitro experiments, including colony formation and transwell assays, and in vivo in nude mouse models. Western blot analysis was used to evaluate the expression levels of proteins associated with epithelial-mesenchymal transition (EMT). LIMT expression was significantly lower in HCC than in normal liver tissue. Functionally, overexpression of LIMT repressed the proliferation, invasion, and EMT of HCC cells, while LIMT knockdown increased proliferation, invasion, and EMT of HCC cells in vitro. Furthermore, LIMT overexpression suppressed HCC growth and metastasis while silencing of LIMT had an opposite effect in vivo. Finally, LIMT overexpression reversed EGF-induced EMT. CONCLUSIONS: Our results suggest that LIMT could play an anti-cancer effect in HCC and might be a potential novel therapeutic target in HCC.

circREEP3 Drives Colorectal Cancer Progression via Activation of FKBP10 Transcription and Restriction of Antitumor Immunity.

Colorectal cancer (CRC) is one of the most common tumors around the world. Circular RNA is widely involved in tumor progression via unclear mechanisms. Here, circREEP3 is found to be upregulated in CRC tissues. circREEP3 upregulation predicts poor patient survival. circREEP3 knockout suppresses CRC tumorigenesis and metastasis, and impairs stem cell-like phenotype. Mechanistically, circREEP3 recruits the chromatin remodeling protein CHD7 to FKBP10 promoter and activates its transcription. Moreover, circREEP3 restricts RIG-1-dependent antitumor immunity. FKBP10 is highly expressed in CRC tissues and associated with poor prognosis. FKBP10 ectopic expression partially rescues the potential of proliferation and metastasis in circREEP3-deficient CRC cells. Thus, the findings support circREEP3-FKBP10 axis drives CRC progression and may be a critical prognostic marker.

Identification of cis-HOX-HOXC10 axis as a therapeutic target for colorectal tumor-initiating cells without APC mutations.

Colorectal cancer (CRC) is one of the most common cancers worldwide, in which adenomatous polyposis coli (APC) mutations are frequently and uniquely observed. Here we find that cis-HOX (circular RNA stabilizing HOXC10) is robustly expressed in colorectal tumor-initiating cells (TICs). cis-HOX knockout decreases colorectal TIC numbers and impairs the self-renewal, tumorigenesis, and metastatic capacities of TICs, whereas cis-HOX overexpression drives colorectal TIC self-renewal and metastasis. Mechanistically, cis-HOX binds to HOXC10 mRNA to attenuate its decay through blocking the K-homology splicing regulatory protein (KSRP)-binding sequence of HOXC10 3' UTR. HOXC10 is highly expressed in colorectal tumors and TICs and triggers Wnt/ß-catenin activation by activating FZD3 expression. HOXC10 inhibitor salinomycin exerts efficient therapeutic effects in APC-wild-type colorectal tumors, but not in tumors with APC nonsense mutations. Therefore, the cis-HOX-HOXC10 pathway drives colorectal tumorigenesis, stemness, and metastasis and serves as a potential therapeutic target for APC-wild-type colorectal tumors.

The Feasibility of Hand-assisted Laparoscopic and Laparoscopic Multivisceral Resection Compared With Open Surgery for Locally Advanced Colorectal Cancer.

BACKGROUND: The role of hand-assisted laparoscopic and pure laparoscopic surgery for locally advanced colorectal cancer invading or adhering to neighboring organs is controversial. This study evaluated the safety and feasibility of laparoscopic multivisceral resection for colorectal cancer. PATIENTS AND METHODS: This study included 201 patients who underwent multivisceral resection for locally advanced colorectal cancer from January 2007 to December 2013 in the Department of General Surgery, Henan Provincial Hospital. Perioperative outcomes and long-time outcomes were compared among hand-assisted laparoscopic, laparoscopic and open resections. RESULTS: Estimated blood loss, wound length, time to the first flatus, and postoperative hospital stay were significantly less or shorter in the hand-assisted laparoscopic surgery (HALS) and laparoscopic surgery group than in open surgery (OS) group. There were no significant differences in tumor size, retrieved lymph nodes, and R0 resection rate of the primary tumor among the 3 groups. Surgeries started as laparoscopic surgery were completed in that manner 76.6% of the time with 10.6% being converted to OS and 12.8% converted to HALS and there were only 2 conversions (2.2%) to OS in the HALS group. No significant difference was noted for overall morbidity rate and reoperation rate among the 3 groups. The overall observed 5-year survival rate was 60.5% in the laparoscopic group, 55.4% in the HALS group, and 47.7% in the open group. There was no significant difference among the 3 groups in the 5-year survival rate. CONCLUSIONS: Hand-assisted laparoscopic and pure laparoscopic multivisceral resection for locally advanced colorectal cancer is safe and feasible in selected patients. HALS can be used judiciously to reduce the rate of conversion to an open procedure and may be a better alternative for laparoscopic approach.

Open Versus Hand-assisted Laparoscopic Total Gastric Resection With D2 Lymph Node Dissection for Adenocarcinoma: A Case-Control Study.

OBJECTIVE: A case-control study was conducted to investigate the feasibility and safety of hand-assisted laparoscopic total gastrectomy (HALTG) with D2 lymphadenectomy for gastric cancer as opposed to traditional open total gastrectomy (OTG). METHODS: One hundred fifty-four patients suffering cardia, upper, middle, or whole gastric cancer operated in our department from February 2009 to February 2012 were divided into 2 groups: the open total gastrectomy group (the OTG group) and the hand-assisted laparoscopic total gastrectomy group (the HALTG group). Operative time, estimated blood loss, number of lymph node retrieval, time to the first flatus, and postoperative hospital stay were compared between the 2 groups. RESULTS: HALTG was associated with significantly less operative blood loss, shorter time to the first flatus and shorter postoperative hospital stay, but longer operative time, compared with OTG. There were no significant differences in tumor size, retrieved lymph nodes, American Joint Committee on Cancer/Union International Control Cancer staging and tumor location between the 2 groups. Negative resection margins were obtained in all patients who had undergone a hand-assisted laparoscopic gastrectomy (100%) and in all but 2 patients in the open group (97.6%). The overall observed 5-year survival rate was 56.5% in the HALTG group and 51.8% in the OTG group (P=0.0001, log-rank test). CONCLUSIONS: HALTG is a safe, feasible, and oncologically sound procedure and has advantages over ODG.

Hand-assisted laparoscopic total gastrectomy with regional lymph node dissection for advanced gastric cancer.

BACKGROUND AND OBJECTIVES: Laparoscopic-assisted distal gastrectomy has been applied to the treatment of gastric cancer. However, there have been few reports on the laparoscopic-assisted total gastrectomy for advanced gastric cancer, mainly because of the difficulty of the procedure. METHODS: Here, we report a series of cases where the hand-assisted laparoscopic total gastrectomies with regional lymph node dissection were performed successfully. RESULTS: The average operative time was 245 minutes. The mean blood loss was 110 mL. The number of dissected lymph nodes per patient was beyond 15 nodes satisfying a reliable evaluation of nodal status. All resection specimens had no residual tumor at the proximal or distal resection margins. The mean oral feeding was 3.6 days. The mean postoperative length of stay was 8.7 days. CONCLUSIONS: The hand-assisted laparoscopic D2 total gastrectomy for advanced gastric cancer is both technically feasible and safe.

Comparison of hand-assisted laparoscopic and open radical distal gastrectomy for obese patients.

To evaluate the feasibility and safety of hand-assisted laparoscopic surgery for gastric cancer in obese patients, we compare the operative outcomes in obese patients who underwent hand-assisted laparoscopic distal gastrectomy (HALDG) and open distal gastrectomy (ODG). One hundred sixty-two obese patients with gastric cancer operated on in our department from January 2009 to December 2011 were divided into two groups: the open distal gastrectomy group (the ODG group) and the hand-assisted laparoscopic distal gastrectomy group (the HALDG group). Operative time, estimated blood loss, number of lymph node retrieval, wound length, times of analgesic injection, time to the first flatus, and postoperative hospital stay were compared between the two groups. Estimated blood loss, wound length, times of analgesic injection, time to the first flatus, and postoperative hospital stay were significantly less or shorter in the HALDG group than in the ODG group. There were no significant differences in tumor size, retrieved lymph nodes, American Joint Cancer Committee /Union Internationale Contre le Cancer staging, and resection margins between the two groups. Obesity should not be seen as a contraindication for HALDG. HALDG for obese patients is a safe, feasible, and oncologically sound procedure and has advantages over ODG.

Hand-assisted laparoscopic spleen-preserving total gastrectomy for gastric cancer: technical feasibility and early results.

To evaluate the feasibility and safety of hand-assisted laparoscopic spleen-preserving total gastrectomy for gastric cancer, we compared the operative outcomes between two methods for dissection of lymph nodes along the distal splenic artery (No. 11d) and at the splenic hilum (No. 10). Sixty-four patients with proximal or total gastric cancer operated on in our department from October 2009 to February 2012 were divided into two groups: the extracorporeal method group (EMG) and the intracorporeal method group (IMG). Operative time, estimated blood loss, number of lymph node retrieval, times of analgesic injection, time to the first flatus, and postoperative hospital stay were compared between the two groups. Estimated blood loss, times of analgesic injection, time to the first flatus, and postoperative hospital stay were equivalent between the two groups. The operative time was significantly shorter in the IMG than the EMG. There were no significant differences in tumor size, retrieved lymph nodes, American Joint Committee on Cancer/Union for International Cancer Control staging, or resection margins between the two groups. Hand-assisted laparoscopic spleen-preserving total gastrectomy is technically feasible and safe and allows for adequate lymphadenectomy.

A hand-assisted laparoscopic distal gastrectomy can be an effective way in obese patients.

OBJECTIVE: To evaluate the feasibility and safety of hand-assisted laparoscopic surgery for gastric cancer in obese patients, we compared the operative outcomes between obese and nonobese patients. METHODS: A total of 114 patients suffering from gastric cancer operated in our department from October 2009 to February 2012 were divided into 2 groups: the obese patients group and the nonobese patients group. RESULTS: Wound length, times of analgesic injection, time to the first flatus, postoperative hospital stay, tumor size, retrieved lymph nodes, AJCC/UICC staging, and resection margins were equivalent between the 2 groups. The estimated blood loss and operative time were significantly less or shorter in the nonobese patients group than in the obese patients group. CONCLUSIONS: Obesity should not be seen as a contraindication for hand-assisted laparoscopic distal gastrectomy, which is a safe and feasible procedure for obese patients.

[The possible causes of serious central nervous system complications occurring after liver transplantation].

OBJECTIVE: To study the classification, possible causes, cure and prevention measures of serious central nervous system (CNS) complications occurring early following liver transplantation. METHODS: The clinical material records of 347 patients undergoing the orthotopic liver transplantation from July 2001 to July 2006 were analyzed retrospectively. The perioperation risk factors of CNS complications, which might be the primary liver disease, serum sodium level, magnesium level, fluctuation degree of plasma osmolality and serum sodium, function of blood clotting, etc. , were analyzed between patients with serious CNS complications and without neurological complications. RESULTS: A total of 71 (20. 46%) neurological symptoms appeared in 347 postoperative patients who included 6 cases (1. 73%) with serious CNS complications such as cerebral edema, cerebral hemorrhage and central pontine myelinolysis, and of 6 cases, 5 patients died. The morbidity of early serious complications of CNS was higher in patients with decompensate cirrhosis and/or hypersplenism. Compared with the group of no neurological complications, two patients with cerebral hemorrhage suffered from preoperative hypersplenism and worse dysfunction of blood clotting (P<0. 05); patients with developed CPM and cerebral oedema had serious hyponatremia history before operation, and intensely fluctuated plasma osmolality showed before and after operation. CONCLUSION: The onset of serious complications of CNS in recipients of liver transplantation may be intimately related to the primary liver disease, and be associated with chronic hyponatremia, rapid correction of serum sodium concentration, intense increase of plasma osmolality and no prompt rectification of the function of blood clotting during perioperation.