Glucose-derived AGEs enhance human gastric cancer metastasis through RAGE/ERK/Sp1/MMP2 cascade Glucose-derived AGEs enhance human gastric cancer metastasis through RAGE/ERK/Sp1/MMP2 cascade

Long non-coding RNAs (lncRNAs) are essential contributors to the progression of various human cancers. Long intergenic non-protein coding RNA 1106 is a member of lncRNAs family. Until now, the specific role of LINC01106 in CRC remains undefined. The aim the current study was to unveil the functions of LINC01106 and explore its potential molecular mechanism in CRC. Based on the data of online database GEPIA, we determined that LINC01106 was expressed at a high level in colon adenocarcinoma (COAD) tissues compared to normal colon tissues. More importantly, high level of LINC01106 had negative correlation with the overall survival of COAD patients. Additionally, we also determined the low level of LINC01106 in normal colon tissues based on UCSC database. Through qRT-PCR, we identified that LINC01106 was highly expressed in CRC tissues compared to adjacent normal ones. Similarly, we detected the expression of LINC01106 and confirmed that LINC01106 was expressed higher in CRC cells than that in normal cells. Subsequently, LINC01106 was mainly distributed in the cytoplasm. LINC01106 induced the proliferation, migration, and stem-like phenotype of CRC cells. Mechanistically, cytoplasmic LINC01106 positively modulated Gli4 in CRC cells by serving as a miR-449b-5p sponge. Furthermore, nuclear LINC01106 could activate the transcription of Gli1 and Gli2 through recruiting FUS to Gli1 and Gli2 promoters. Mechanism of investigation unveiled that Gli2 was a transcription activator of LINC01106. In conclusion, Gli2-induced upregulation of LINC01106 aggravates CRC progression through upregulating Gli2, Gli2, and Gli4.

Aim. To evaluate the impact of preoperative anemia (POA) on perioperative outcomes in patients undergoing elective surgery for colorectal cancer (CRC).Methods. A total of 326 CRC patients were enrolled. POA was defined as a hemoglobin (Hb) concentration ≤ 12 g/dl. Univariable and multivariable analyses were performed to assess the impact of POA on the risks of postoperative complications like surgical site infection (SSI).Results. Patients with colon cancer presented higher rate of POA than patients with rectal cancer (60% versus 40% for colon cancer versus rectal cancer). In addition, female patients and patients with large tumor mass (>4 cm) had a higher rate of POA than male patients and patients with small tumor (≤4 cm), respectively. Upon univariable analysis, CRC patients with POA had a higher rate of incisional SSI than patients without POA (12% versus 6%,P=0.04). However, POA was not associated with other postoperative complications, like anastomotic leak, organ space SSI, and bleeding. Upon multivariable analysis, POA and stoma formation were identified as two independent risk factors for incisional SSI (OR (95%CI): 2.44 (1.09–5.49) for POA versus no POA and 2.64 (1.20–5.81) for stoma formation versus no stoma formation).Conclusions. POA was an independent risk factor for incisional surgical site infection after colorectal resection for CRC, and correcting POA should be considered before elective surgery.

Adipose-derived mesenchymal stem cells (ADMSCs) have been used for treating tissue injury, and preactivation enhances their therapeutic effect. This study is aimed at investigating the therapeutic effect of activated ADMSCs by IL-1β on the intestinal ischaemia-reperfusion (IR) injury and exploring potential mechanisms. ADMSCs were pretreated with IL-1β in vitro, and activation of ADMSCs was assessed by α-SMA and COX-2 expressions and secretary function. Activated ADMSCs was transplanted into IR-injured intestine in a mouse model, and therapeutic effect was evaluated. In addition, to explore underlying mechanisms, COX-2 expression was silenced to investigate its role in activated ADMSCs for treatment of intestinal IR injury. When ADMSCs were pretreated with 50 ng/ml IL-1β for 24 hr, expressions of α-SMA and COX-2 were significantly upregulated, and secretions of PGE₂, SDF-1, and VEGF were increased. When COX-2 was silenced, the effect of IL-1β treatment was abolished. Activated ADMSCs with IL-1β significantly suppressed inflammation and apoptosis and enhanced healing of intestinal IR injury in mice, and these effects were impaired by COX-2 silencing. The results of RNA sequencing suggested that compared with the IR injury group activated ADMSCs induced alterations in mRNA expression and suppressed the activation of the NF-κB-P65, MAPK-ERK1/2, and PI3K-AKT pathways induced by intestinal IR injury, whereas silencing COX-2 impaired the suppressive effect of activated ADMSCs on these pathway activations induced by IR injury. These data suggested that IL-1β pretreatment enhanced the therapeutic effect of ADMSCs on intestinal IR injury repairing via activating ADMSC COX-2-PGE₂ signaling axis and via suppressing the NF-κB-P65, MAPK-ERK1/2, and PI3K-AKT pathways in the intestinal IR-injured tissue.