Metformin suppresses proliferation and glycolysis of gastric cancer by modulating ADAMTS12.

BACKGROUND: Gastric cancer (GC) is a common malignancy with its morbidity increasing worldwide. Hence, it is imperative to develop effective treatments. Studies have shown that metformin has potential antitumor effects. The objective of this study was to probe the antitumor mechanism of metformin in GC. METHODS: The expression of ADAMTS12 in GC tissues and its enrichment pathways were analyzed by bioinformatics methods. ADAMTS12 expression in GC cells was assessed by qRT-PCR. Cell viability and proliferation were analyzed by CCK-8 and colony formation assays, respectively. Extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) of GC cells in different treatment groups were analyzed by Seahorse XP 96, and glycolysis metabolites were detected by corresponding kits. Western blot was employed to analyze the level of glycolysis pathway related protein HK-2, and cell functional assays were conducted to verify the functions of metformin on GC cells. A xenograft model was constructed to validate the inhibitory role of metformin in GC. RESULTS: ADAMTS12 expression was elevated in GC tissues/cells and concentrated in glycolysis pathway. Cell functional assays found that ADAMTS12 promoted the proliferation and glycolysis of GC cells. Rescue experiments showed that metformin could reduce the promoting effect of ADAMTS12 overexpression on the proliferation and glycolysis of GC cells. In vivo studies confirmed that metformin suppressed the proliferation and glycolysis process via ADAMTS12 in GC cells. CONCLUSION: Metformin can repress the proliferation and glycolysis of GC cells via ADAMTS12. The results suggest the potential of ADAMTS12 being a target for the metformin therapy of GC.

Prognostic value of oxidative stress-related genes in colorectal cancer and its correlation with tumor immunity.

Oxidative stress (OS) plays an essential role in chronic diseases such as colorectal cancer (CRC). In this study, we aimed to explore the relation between oxidative stress-related genes and CRC prognosis and their involvement in the immune microenvironment. Totally 101 OS-related genes were selected from the MsigDB database. Then, univariate Cox regression was used to explore the prognostic value of the selected genes correlated with the CRC patient survival in the TCGA database. A total of 9 prognostic OS-related genes in CRC were identified. Based on consensus clustering, CRC patients were then categorized into two molecular subtypes. A prognostic risk model containing 8 genes was established using Lasso regression, and CRC patients were divided into high or low-risk groups based on the median risk scores. The predictive value of the 8 genes in CRC prognosis was validated using ROC curves, which indicate that CTNNB1, STK25, RNF112, SFPQ, MMP3, and NOL3 were promising prognostic biomarkers in CRC. Furthermore, the immune cell infiltration levels in different risk groups or CRC subtypes were analyzed. We found that the high-risk or C1 subtype had immunosuppressive microenvironment, which might explain the unfavorable prognosis in the two groups of CRC patients. Additionally, functional experiments were conducted to investigate the effects of OS-related genes on CRC cell proliferation, stemness, and apoptosis. We found that CTNNB1, HSPB1, MMP3, and NOL3 were upregulated in CRC tissues and cells. Knockdown of CTNNB1, HSPB1, MMP3, and NOL3 significantly suppressed CRC cell proliferation, stemness and facilitated CRC cell apoptosis. In conclusion, we established prognostic CRC subtypes and an eight-gene risk model, which may provide novel prognostic indicators and benefit the design of individualized therapeutic strategies for CRC patients.

Efficacy of robot-assisted vs. laparoscopy surgery in the treatment of colorectal cancer: A systematic review and meta-analysis.

PURPOSE: To compare the efficacy of robot-assisted colorectal surgery (RACS) vs. laparoscopic-assisted colorectal surgery (LACS) in the treatment of colorectal cancer (CRC). METHODS: PubMed, Embase, and the Cochrane Library databases were systematically searched for randomized controlled trials (RCTs) reporting on RACS and LACS in CRC patients published up to January 4, 2022. The outcomes included operative time, length of stay, conversion, circumferential resection margin positivity (CRM+), and complications. RESULTS: Six RCTs (412 participants with RACS and 420 with LACS) were included. The pooled results showed shorter operative time (WMD=44.28, 95%CI: 9.36, 79.19, P = 0.013; PQ<0.001) and lower costs in RACS than in LACS (WMD=1546.15, 95%CI: 761.51, 2330.78, P<0.001; PQ=0.208), while no differences were observed for the length of stay (WMD=-0.31, 95%CI: -1.13,0.51, P = 0.456; I2=0.0%, PQ=0.990), blood loss (WMD=-33.72, 95%CI: -205.06, 137.62, P = 0.700; I2=89.0%, PQ=0.003), the number of harvested lymph nodes (WMD=1.38, 95%CI: -0.09, 2.85, P = 0.066; I2=0.0%, PQ=0.645), the time of first flatus (WMD=0.20, 95%CI: -0.20, 0.61, P = 0.328; I2=0.0%, PQ=0.337), rates of conversion to open surgery (RR=0.62, 95%CI: 0.38,1.01, P = 0.053; I2=0.0%, PQ=0.459), complication rates (RR=1.11, 95%CI: 0.83,1.49, P = 0.466; I2=0.0%, PQ=0.948), and CRM+ rates (RR=1.02, 95%CI: 0.66,1.58, P = 0.938; I2=0.0%, PQ=0.408). No publication bias was detected. The sensitivity analyses showed that the results for the operative time were robust. CONCLUSIONS: Patients with CRC who underwent RACS and LACS had a similar length of stay, blood loss, the time of first flatus, rates of conversion to open surgery, the number of harvested lymph nodes, complication rates, and CRM+ rates; however, RACS led to longer surgeries and higher costs than LACS.

Mesenchymal Stem Cell-Derived Exosomes are Effective for Radiation Enteritis and Essential for the Proliferation and Differentiation of Lgr5+ Intestinal Epithelial Stem Cells by Regulating Mir-195/Akt/ß-Catenin Pathway.

BACKGROUND: Radiation enteritis (RE) is a common complication of abdominal or pelvic radiotherapy, which when severe, could be life-threatening. Currently, there are no effective treatments. Studies have shown that mesenchymal stem cells (MSCs)-derived exosomes (MSC-exos) exhibit promising therapeutic effects in inflammatory diseases. However, the specific role of MSC-exos in RE and the regulatory mechanisms remain elusive. METHODS: In vivo assay was carried out by injecting MSC-exos into the total abdominal irradiation (TAI)-induced RE mouse model. For in vitro assay, Lgr5-positive intestinal epithelial stem cells (Lgr5+ IESC) were extracted from mice, followed by irradiation along with MSC-exos treatment. HE staining was performed to measure histopathological changes. mRNA expression of inflammatory factors TNF-α and IL-6 and stem cell markers LGR5, and OCT4 were quantified by RT-qPCR. EdU and TUNEL staining was performed to estimate cell proliferation and apoptosis. MiR-195 expression in TAI mice and radiation-induced Lgr5+ IESC was tested. RESULTS: We found that the injection of MSC-exos inhibited inflammatory reaction, increased stem cell marker expression, and maintained intestinal epithelial integrity in TAI mice. Furthermore, MSC-exos treatment increased the proliferation and simultaneously suppressed apoptosis in radiation-stimulated Lgr5+ IESC. MiR-195 expression increased by radiation exposure was decreased by MSC-exos therapy. MiR-195 overexpression facilitated the progress of RE by counteracting the effect of MSC-exos. Mechanistically, the Akt and Wnt/ß-catenin pathways inhibited by MSC-exos were activated by miR-195 upregulation. CONCLUSION: MSC-Exos are effective in treating RE and are essential for the proliferation and differentiation of Lgr5+ IESCs. Moreover, MSC-exos mediates its function by regulating miR-195 Akt ß-catenin pathways.

Relationship between inferior mesenteric artery diameter and rectal cancer.

Introduction: A dilated inferior mesenteric vein has been reported in rectal cancer patients. However, no study has yet reported inferior mesenteric artery (IMA) enlargement in rectal cancer. We aimed to assess the relationship between the IMA diameter and rectal cancer. Material and methods: Patients diagnosed with rectal cancer and a control group of 42 patients in our hospital from July 2017 to June 2019 were evaluated. The IMA diameter was independently measured by two observers on axial computed tomography images. Results: The mean IMA diameter was wider in rectal cancer patients (2.49 ±0.53 mm) than in the control group (2.20 ±0.47 mm, p < 0.001). The IMA diameter of patients with stage I, stage II, stage III, and stage IV cancers was 2.24 ±0.36 mm, 2.45 ±0.39 mm, 2.80 ±0.55 mm, and 2.85 ±0.51 mm, respectively (p < 0.001). The IMA diameter correlated positively and moderately with TNM stage (r = 0.519, p < 0.001). The IMA diameter of patients with T1, T2, T3, and T4 tumors was 2.18 ±0.31 mm, 2.39 ±0.50 mm, 2.55 ±0.48 mm, and 2.73 ±0.51 mm, respectively (p < 0.001). The IMA diameter also correlated positively and moderately with T stage (r = 0.457, p < 0.001). The IMA diameter of patients with N0, N1, and N2 tumors was 2.37 ±0.39 mm, 2.83 ±0.60 mm, and 2.71 ±0.40 mm, respectively (p < 0.001); however, the IMA diameter did not correlate with N stage (r = 0.166, p = 0.077). Patients with M1 tumors had a wider IMA diameter than patients with M0 tumors (p = 0.011). Conclusions: The IMA in rectal cancer patients enlarges as the TNM stage gets higher. The IMA diameter can be accepted as a possibly important marker for the staging of rectal cancer.

MEX3A promotes angiogenesis in colorectal cancer via glycolysis.

As a gastrointestinal malignancy, colorectal cancer (CRC) is a main cause of cancer-related deaths worldwide. Mex-3 RNA-binding family member A (MEX3A) is upregulated in multiple types of tumors and plays a critical role in tumor proliferation and metastasis. However, the function of MEX3A in CRC angiogenesis has not been fully understood. Hence, the aim of this study was to explore the role of MEX3A in CRC angiogenesis and investigate its underlying mechanisms. MEX3A expression in CRC was first investigated by bioinformatics means and then measured by qRT-PCR and Western blot. CCK-8 assay was employed to test cell viability. Angiogenesis assay was used to assess angiogenesis. The protein levels of VEGF, FGF and SDF-1 were evaluated using Western blot. The expression levels of MYC, HK2 and PGK1 were investigated by qRT-PCR. Extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) were determined by Seahorse XP 96. The levels of pyruvate, lactate, citric acid and malate were measured by corresponding kits. Bioinformatics analysis demonstrated high MEX3A expression in CRC tissues and MEX3A enrichment in glycolysis and angiogenesis pathways. Cell assays showed high MEX3A expression in CRC cells and its promoting effects in CRC cell proliferation and glycolysis as well as angiogenesis. Rescue experiment confirmed that glycolysis inhibitor 2-DG could offset the promoting effects of MEX3A on the proliferation, angiogenesis and glycolysis of CRC cells. In conclusion, MEX3A could facilitate CRC angiogenesis by activating the glycolytic pathway, suggesting that MEX3A may be a novel therapeutic target for CRC.

Recurrent Bleeding From a Duodenal Ulcer Halted by Laparoscopic Oversewing Under Endoscopic Guidance.

Peptic ulcers are the most common causes of upper gastrointestinal bleeding. Although most peptic ulcer bleeding can be controlled by medical and endoscopic treatment, a small number of patients with recurrent bleeding eventually require surgical treatment. In recent years, laparoscopy, a minimally invasive surgical method, has gained popularity and acceptance. We, herein, report a case of recurrent duodenal ulcer bleeding. Laparoscopic oversewing of the bleeding ulcer under endoscopic guidance resulted in satisfactory recovery. We suggest that for recurrent bleeding from peptic ulcers, laparoscopic oversewing under endoscopic guidance should be recommended as a possible early option to halt the bleeding. Key Words: Upper gastrointestinal bleeding, Peptic ulcer, Laparoscopy, Treatment.

Clinical outcomes of endoscopic versus laparoscopic resection for senile patients with gastric gastrointestinal stromal tumours (2 to 4 cm) originating from the muscularis propria layer.

Introduction: Currently, there still are no selection criteria for endoscopic resection (ER) versus laparoscopic resection (LR) of gastric gastrointestinal stromal tumours (GIST) (2 to 4 cm) originating from the muscularis propria layer (MP-GISTs). Aim: To investigate and compare the long-term prognosis of ER and LR for resecting gastric MP-GISTs, with at least 5 years of follow-up. Material and methods: Between January 2010 and December 2015, 134 patients with gastric MP-GISTs were consecutively enrolled in this study. The main comparison measurements included the short-term and long-term outcomes between the ER group (n = 89) and the LR group (n = 45). Results: In this study, there were no significant differences in the rates of complete resection (p = 0.220) and short-term complications (p = 0.663) between the ER group and the LR group. The ER group had a shorter operation time (50.1 ±18.2 min vs. 120.6 ±32.5 min, p < 0.001), shorter hospital stays (5.1 ±1.9 days vs. 6.4 ±3.7 days, p = 0.026), and lower hospitalization costs (16639.5 ±5091.3 CNY vs. 24030.4 ±6803.1 CNY, p < 0.001) than the LR group. The ER group had a lower rate of long-term complications than the LR group (p = 0.001) during the follow-up period (84.2 ±17.9 months vs. 89.0 ±16.8 months, p = 0.207). Conclusions: Our results showed that ER was a more feasible treatment approach than LR when the gastric MP-GIST was located in or near the cardia/pylorus. ER also had several other advantages over LR, such as a shorter procedure time, shorter hospital stay, and lower hospitalization costs.

Esophageal Mucosal Autograft for Preventing Stricture After Widespread Endoscopic Submucosal Dissection of Superficial Esophageal Lesions.

BACKGROUND: Although esophageal mucosal autograft prevents esophageal stricture after widespread endoscopic submucosal dissec- tion and has been reported as a new technique, it is relatively unproven in clinical practice. This prospective study was conducted to evaluate our experience using esophageal mucosal autograft to prevent strictures after widespread endoscopic submucosal dissection in patients with widespread superficial esophageal lesions. METHODS: Between October 2017 and June 2018, 15 patients with widespread superficial esophageal lesions were consecutively treated with widespread endoscopic submucosal dissection and then underwent esophageal mucosal autograft. The main outcomes measured included esophageal epithelialization and esophageal stricture. RESULTS: The median longitudinal diameter of the widespread superficial esophageal lesions was 5.2 cm. All 15 patients were success- fully treated with widespread endoscopic submucosal dissection and esophageal mucosal autograft, and the median procedural time was 182 minutes. During follow-up (median, 23 months), esophageal epithelialization was found in 13 patients (86.7%), and 7 patients experienced esophageal stricture (46.7%). In those 7 patients, the esophageal strictures were successfully relieved after endoscopic bal- loon dilation or endoscopic radial incision. No complications related to endoscopic balloon dilation/endoscopic radial incision occurred. Additionally, local recurrence was found in 1 patient with poorly differentiated squamous cell carcinoma, and further surgical resection was performed. CONCLUSIONS: Esophageal mucosal autograft appears to be an efficient approach to reconstructing local esophageal epithelium and might have a potential role in preventing esophageal stricture after widespread endoscopic submucosal dissection. However, as a new technique, it needs more improvement to enhance its role in preventing esophageal stricture after widespread endoscopic submucosal dissection.

MiR-1-3p targets CENPF to repress tumor-relevant functions of gastric cancer cells.

Here we noted significantly downregulated miR-1-3p in gastric cancer (GC) tissue compared with adjacent normal tissue through qRT-PCR. Lowly expressed miR-1-3p correlated GC progression. Overexpressing miR-1-3p could restrain tumor-relevant cell behaviors in GC, while miR-1-3p inhibitor treatment triggered the opposite results. Moreover, dual-luciferase reporter gene detection identified specific binding sites of miR-1-3p in CENPF 3'untranslated region. Upregulating miR-1-3p constrained cell progression of GC via CENPF downregulation. Western blot, qRT-PCR and dual-luciferase detections manifested that miR-1-3p negatively mediated CENPF expression in GC cells. Thus, we demonstrated that miR-1-3p negatively mediated CENPF to hamper GC progression. CENPF may be an underlying target for GC therapy.

Difficult Defecation Caused by a Huge Rectal Leiomyoma.

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Targeting AURKA by microRNA-490-3p suppresses gastric cancer cell growth.

OBJECTIVE: To illustrate the molecular mechanism of microRNA-490-3p regulating gastric cancer (GC) cells by targeting AURKA. METHODS: Genes with significantly different expression in GC and normal tissue in TCGA-STAD dataset were analyzed by bioinformatics. Expression levels of genes and proteins in GC cells were measured by qRT-PCR and western blot. The interaction between microRNA-490-3p and AURKA was verified by dual luciferase assay. Proliferation, migration, invasion and apoptosis of GC cells were evaluated through a set of cell function assays. RESULTS: MicroRNA-490-3p was significantly less expressed in GC, while AURKA was significantly highly expressed. Dual luciferase reporter gene assay proved that microRNA-490-3p targeted AURKA. Up-regulation of microRNA-490-3p restrained proliferation, migration, invasion and stimulated apoptosis of GC cells, which was attenuated by overexpression of AURKA. CONCLUSIONS: MicroRNA-490-3p was likely to restrain the development of GC cells by inhibiting AURKA, and it may be an underlying target for GC treatment.

Billroth-II with Braun versus Roux-en-Y reconstruction in totally laparoscopic distal gastrectomy for gastric cancer.

INTRODUCTION: Totally laparoscopic distal gastrectomy (TLDG) has been increasingly adopted for the treatment of gastric cancer. Both Billroth-II with Braun (B-IIB) reconstruction and Roux-en-Y (R-Y) reconstruction are commonly performed in TLDG; however, which of these reconstruction techniques is better remains unclear. AIM: To compare the efficacy of B-IIB reconstruction and R-Y reconstruction in TLDG for gastric cancer. MATERIAL AND METHODS: A total of 105 gastric cancer patients who underwent TLDG with B-IIB or R-Y reconstruction were reviewed from January 2019 to July 2020. Clinicopathological characteristics and perioperative data of the B-IIB and R-Y groups were compared. RESULTS: Clinicopathological characteristics were not significantly different between the B-IIB and R-Y groups. The average total operative time for the R-Y group (161.9 ±20.7 min) was significantly longer than that for the B-IIB group (141.9 ±16.7 min). The average anastomosis time for the R-Y group (25.5 ±4.1 min) was also significantly longer than that for the B-IIB group (18.9 ±3.3 min). Blood loss volume, number of retrieved lymph nodes, time to first flatus, average length of postoperative hospital stay, inflammatory parameters and postoperative complications did not differ between the two groups. CONCLUSIONS: Both B-IIB reconstruction and R-Y reconstruction are safe and effective in TLDG. B-IIB reconstruction is easier and faster to perform than R-Y reconstruction in TLDG.

Deubiquitination and Stabilization of PD-L1 by USP21.

Recent studies have shown that the expression level of PD-L1 in tumor cells positively correlates with tumor metastasis and recurrence rate. The effects of post-translational modifications (PTMs) of PD-L1 are related to immunosuppression. However, the degradation of PD-L1 in cancers has not yet been sufficiently defined. Here, we identified USP21 as a novel deubiquitinase of PD-L1. Overexpression of USP21 significantly increased PD-L1 abundance while its knockdown induced PD-L1 degradation. In vitro deubiquitination assay revealed that USP21-WT, but not USP21-C221A, reduced polyubiquitin chains of PD-L1. These results highlight the role of USP21 in the deubiquitination and stabilization of PD-L1. Furthermore, we show that USP21 is the frequently amplified deubiquitinase in lung cancer, especially in lung squamous cell carcinoma, and its amplification is accompanied by upregulation of PD-L1. This study reveals the mechanism of USP21-mediated PD-L1 degradation, and suggests that USP21 might be a potential target for the treatment of lung cancer.

ABAT targeted by miR-183-5p regulates cell functions in liver cancer.

BACKGROUND: Liver cancer triggers a considerable number of global deaths. This work focused on mechanisms as well as impacts of ABAT in liver cancer. METHODS: Differentially expressed mRNAs in liver cancer were analyzed with The Cancer Genome Atlas (TCGA) database to determine and evaluate the prognostic significance of the target gene ABAT. ABAT was overexpressed to explore its effect on liver cancer. Furthermore, the targeted regulation between miR-183-5p and ABAT was verified through dual-luciferase method. The effects of their expression on liver cancer functions were detected by cell functional experiments like Cell Counting Kit-8 (CCK8), Transwell and flow cytometry. Lastly, the inhibitory effect of ABAT on the tumor was proved in nude mice in vivo. RESULTS: At tissue and cell levels, ABAT was inactivated in liver cancer, and liver cancer patients with lowly expressed ABAT had poor prognosis. Overexpressing ABAT could inhibit cancer cell behaviors, and suppress tumorigenesis in nude mice. Meanwhile, overexpressed ABAT could upregulate E-cadherin in liver cancer cells, while downregulate MMP-9, Vimentin, MMP-2, N-cadherin, Ki67. Of note, miR-183-5p was highly expressed in liver cancer tissue and cells, which could target and downregulate ABAT expression. It was indicated by rescue assay that lowly expressed miR-183-5p could repress functions of liver cancer cells, while such inhibitory effect could be recovered by ABAT silencing. CONCLUSION: Downstream of miR-183-5p, ABAT was targeted to mediate progression of liver cancer.

CircRASSF2 facilitates the proliferation and metastasis of colorectal cancer by mediating the activity of Wnt/ß-catenin signaling pathway by regulating the miR-195-5p/FZD4 axis.

Circular RNAs (circRNA) are a key regulator of cancer progression, including colorectal cancer (CRC). Nevertheless, the role of circRASSF2 in CRC remains unclear. Quantitative real-time PCR was used to measure the expression of circRASSF2 and miR-195-5p. Cell counting kit 8 assay, colony formation assay, flow cytometry and transwell assay were used to determine the proliferation, apoptosis, migration and invasion of cells, respectively. The levels of proliferation, metastasis and Wnt/ß-catenin signaling pathway-related proteins, as well as Frizzled 4 (FZD4) protein, were determined using western blot analysis. Furthermore, a dual-luciferase reporter assay, RNA immunoprecipitation assay and RNA pull-down assay were used to illumine the mechanism of circRASSF2. Animal experiments were used to determine the role of circRASSF2 in the tumor growth of CRC in vivo. Our study reported that circRASSF2 was upregulated in CRC tissues and cells, and its high expression was related to the poor prognosis of CRC patients. CircRASSF2 knockdown could inhibit proliferation, migration, invasion, and enhance apoptosis in CRC cells, and its overexpression had the opposite effect. Besides, our data revealed that circRASSF2 could sponge miR-195-5p, and miR-195-5p could target FZD4. The rescue experiments indicated that both miR-195-5p inhibitor and FZD4 overexpression could reverse the negative regulation of circRASSF2 silencing on CRC progression. Moreover, circRASSF2 could positively regulate the activity of Wnt/ß-catenin signaling pathway by the miR-195-5p/FZD4 axis. In addition, circRASSF2 knockdown restrained the tumor growth of CRC in vivo. Our findings suggested that circRASSF2 might function as a tumor promoter to accelerate the progression of CRC via regulating the miR-195-5p/FZD4/Wnt/ß-catenin pathway.

Endoscopic resection of large (≥ 4 cm) upper gastrointestinal subepithelial tumors originating from the muscularis propria layer: a single-center study of 101 cases (with video).

BACKGROUND AND AIMS: Although endoscopic resection (ER) is already established as a minimally invasive technique for small (< 4.0 cm) upper gastrointestinal subepithelial tumors originating from the muscularis propria layer (MP-SETs), published data of ER for large (≥ 4.0 cm) upper gastrointestinal MP-SETs are extremely rare and limited to case reports. This retrospective study aimed to evaluate the feasibility and safety of ER for large (≥ 4.0 cm) upper gastrointestinal MP-SETs in a large case series. METHODS: Between June 2012 and December 2018, 101 patients with large (≥ 4 cm) upper gastrointestinal MP-SETs were enrolled in this study. The main outcome measures included complete resection, total complications, and local residual or recurrent tumor. RESULTS: The rate of complete resection was 86.1%. Thirteen patients (12.9%) experienced complications including gas-related complications (6/101, 5.9%), localized peritonitis (4/101, 4.0%), esophageal/cardiac mucosal laceration (2/101, 2.0%), and delayed bleeding (1/101, 1.0%). These 13 patients recovered after endoscopic and conservative treatment. The independent risk factor for incomplete resection was tumor size (P = 0.005), and the independent risk factors for total complications were tumor size (P = 0.011) and tumor extraluminal growth (P = 0.037). During the median follow-up of 36 months, local residual tumor was detected in 1 patient. No local recurrence occurred in any patient. CONCLUSIONS: Despite being associated with a relatively low complete resection rate, ER is an alternative therapeutic method for large (≥ 4.0 cm) upper gastrointestinal MP-SETs when performed by an experienced endoscopist. This method is especially valuable for patients who are unwilling to undergo surgery.

LncRNA BLACAT1/miR-519d-3p/CREB1 Axis Mediates Proliferation, Apoptosis, Migration, Invasion, and Drug-Resistance in Colorectal Cancer Progression.

BACKGROUND: Colorectal cancer (CRC) is a common severe disease around the world. The merging papers reported that long noncoding RNAs (lncRNAs) took part in the diversified pathological processes of CRC. This study aimed to uncover the role and the potential mechanism of lncRNA bladder cancer-associated transcript 1 (BLACAT1) in CRC progression. METHODS: LncRNA BLACAT1, micro-519d-3p (miR-519d-3p), and cAMP-responsive element binding protein 1 (CREB1) levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR) in CRC tissues and cells. The bio-functional effects were examined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), flow cytometry assay, and transwell assay. The susceptibility testing was determined by oxaliplatin (OXA) administration. The potential binding sites between miR-519d-3p and BLACAT1 or CREB1 were predicted by online software starBase and confirmed by dual-luciferase reporter analysis. The relative proteins expression in CRC cells was determined by Western blot analysis. Xenograft tumor model was used to evaluate biological function of BLACAT1 in vivo. RESULTS: The expression of BLACAT1 was promoted in CRC tissues and cells, and correlated to the TNM (tumor, node, metastasis) stage, distant metastasis, and overall survival rate. Silencing of BLACAT1 limited the proliferation, migration, and invasion, facilitated the apoptosis, and re-sensitized OXA-resistance in CRC cells. MiR-519d-3p was a target of BLACAT1. Furthermore, miR-519d-3p deletion reversed the positive effects of BLACAT1 deletion on CRC cells. Moreover, our data showed that miR-519d-3p directly targeted CREB1 and BLACAT1 sponged miR-519d-3p to regulate CREB1 expression. Besides, CREB1 disrupted the bio-functional results above from BLACAT1 suppression. Additionally, BLACAT1 knockdown promoted CRC cells sensitivity to OXA in vivo. CONCLUSION: BLACAT1 mediated the progression of CRC and OXA-resistance by miR-519d-3p/CREB1 axis.