Circ-MALAT1 accelerates cell proliferation and epithelial mesenchymal transformation of colorectal cancer through regulating miR-506-3p/KAT6B axis.

Colorectal cancer (CRC) is a prevalent malignant tumor of the digestive tract. Circular RNAs may play important roles in the progression of CRC. In this study, we investigated the roles and mechanisms of action of circ-MALAT1 in CRC. Gene expression and protein abundance were determined using qRT-PCR and western blot, respectively. Cell proliferation and migration were assessed by MTT, clone formation, and wound-healing assays. The interactions among the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (circ-MALAT1), miR-506-3p, and lysine acetyltransferase 6B (KAT6B) were predicted using the StarBase software and confirmed by the luciferase activity assay. Circ-MALAT1 and KAT6B were upregulated, while miR-506-3p was downregulated in CRC cells. We validated that knocking down of circ-MALAT1 suppressed proliferation, migration, and epithelial-mesenchymal transition (EMT) of CRC cells, and these effects were abolished by miR-506-3p downregulation or KAT6B sufficiency. Our study suggests that circ-MALAT1 could sponge miR-506-3p to regulate the expression of KAT6B. Moreover, KAT6B sufficiency could neutralize miR-506-3p-dependent growth arrest, migration, and EMT. Circ-MALAT1 promotes cell proliferation, migration, and EMT of CRC cells via the miR-506-3p/KAT6B axis, thereby acting as a novel potential therapeutic target for the treatment of colorectal cancer.

CircPTK2 accelerates tumorigenesis of colorectal cancer by upregulating AKT2 expression via miR-506-3p.

With the rapid increase in its incidence in the last decade, colorectal cancer (CRC) is becoming one of the most life-threatening cancers. Circular RNA PTK2 (circPTK2) has multiple functions in oncogenesis, including in CRC. However, it remains elusive if circPTK2 also plays an important role in CRC malignancy. The levels of circPTK2, miR-506-3p, and AKT serine/threonine kinase 2 (AKT2) were measured by qPCR. The protein level of AKT2 was evaluated by western blotting assay. The proliferation, migration, and invasion of CRC cancer cells were evaluated by MTT, colony formation, wound-healing, and transwell assays. The interaction between circPTK2 and miR-506-3p and between miR-506-3p and AKT2 mRNA were verified by dual-luciferase reporter assay. The expressions of circPTK2 and AKT2 were elevated in CRC cells, with a concomitant reduction of miR-506-3p. The knockdown of circPTK2 suppressed the proliferation, migration, and invasion of CRC cells. CircPTK2 targeted miR-506-3p and negatively regulated its expression. Furthermore, miR-506-3p overexpression suppressed the CRC progression by downregulating the AKT2 expression. AKT2 overexpression or miR-506-3p inhibition restored the suppression of growth and invasiveness of CRC cancer cells caused by circPTK2 silencing. The circPTK2/miR-506-3p/AKT2 axis plays a novel and essential role in promoting CRC progression, providing potential targets for CRC therapeutic modality.

LINC00657 regulate colorectal carcinoma invasion and migration by enhancing heparanase expression through recruiting SMAD family member 2.

Long noncoding RNAs are master regulators of several cancer phenotypes, such as cell growth, apoptosis, and motility. This study is designed to resolve the relevance of LINC00657 with tumor invasion and migration and its action mechanism in colorectal carcinoma (CRC). LINC00657 and HPSE levels were first examined in cancerous tissues from CRC patients and CRC cells. Then functional experiments were conducted to evaluate the abilities of HCT116 and SW620 cells to proliferate, migrate, and invade when LINC00657 or HPSE was knocked down, or LINC00657 knockdown and SMAD2 overexpression were simultaneously introduced. Snail and E-cadherin levels in the CRC cells were evaluated. Next, the binding between LINC00657 and SMAD2 or between SMAD2 and HPSE was determined. LINC00657-silencing HCT116 cells were inoculated into nude mice, and the tumorigenesis and the levels of Snail and E-cadherin were evaluated. LINC00657 and HPSE were increasingly expressed in CRC. Knockdown of LINC00657 or HPSE inhibited the malignant properties of CRC cells, decreased Snail expression, and strengthened E-cadherin level. LINC00657 and HPSE could both bind to SMAD2. SMAD2 overexpression counteracted the inhibiting effect of LINC00657 silencing on HPSE expression and the growth and invasion of CRC cells. In vivo experiments further verified the suppression of LINC00657 knockdown on tumor growth and metastasis. LINC00657 recruits SMAD2 to HPSE promoter region to elevate HPSE transcription, thus accelerating CRC invasion and migration.

SIRT6 promotes ferroptosis and attenuates glycolysis in pancreatic cancer through regulation of the NF-κB pathway.

Pancreatic cancer (PC) is a malignant tumor with high mortality worldwide. SIRT6 plays versatile roles in human cancers. However, SIRT6 has rarely been studied in PC. The purpose of the present study was to explore the function and potential mechanism of SIRT6 in PC. The expression of SIRT6 in PC tissues and cells was detected by reverse transcription-quantitative PCR and western blotting. The overall survival time was analyzed through the Kaplan Meier method. Cell viability was measured by the Cell Counting Kit-8 assay. The Fe2+ content, glucose uptake, lactic acid and ATP production were detected through the corresponding kits. ROS was evaluated using the DCFH-DA detection kit. Protein expression was assessed by immunohistochemistry or western blot analysis. In the present study, SIRT6 was lowly expressed in PC tissues and cells compared with normal tissues and cells. Moreover, the low expression of SIRT6 was associated with a poor prognosis in patients with PC. Upregulation of SIRT6 significantly promoted the ferroptosis and inhibited the glycolysis in PC cells. However, knockdown of SIRT6 resisted ferroptosis and increased glycolysis in PC cells. Further studies found that the activation of NF-κB could reverse the effect of SIRT6 on PC cells. In addition, overexpression of SIRT6 restrained the growth of xenografted tumors and suppressed the nuclear transcription of NF-κB in vivo. Collectively, the present study indicated that SIRT6 promoted ferroptosis and inhibited glycolysis through inactivating the NF-κB signaling pathway in PC. These findings suggested that SIRT6 may become a therapeutic target for PC.

Transanal endoscopic microsurgery for radical resection of sigmoid cancer.

PURPOSE: This study aimed to investigate the efficacy and safety of transanal endoscopic microsurgery for radical resection of sigmoid cancer. METHODS: 91 patients with sigmoid cancer who underwent sigmoid cancer resection were divided to the Control Group (43 patients who underwent conventional laparoscopic surgery and pathological specimens were taken through the abdomen) and the Study Group (48 patients who were subjected to transanal endoscopic microsurgery and pathological specimens were taken through the anus). Comparisons were made about the operation time and the amount of surgical bleeding of the two groups, as well as the postoperative exhaust time and postoperative visual analogue score (VAS) of the two groups. Also, factors like the complications, postoperative hospitalization time, additional analgesic treatment, and treatment efficacy of patients within the first month after the surgery were compared between the two groups. Finally, a 3-year follow up for patients was performed to record the 3-year recurrence rates. RESULTS: The operation time and the amount of surgical bleeding of the Study Group were significantly lower than those of the Control Group (p<0.05); the 3-year recurrence rate of the Study Group was lower than that of the Control Group. On the contrary, the 3-year survival rate of the Study Group was significantly higher than that of the Control Group (p<0.05). CONCLUSION: The application of transanal endoscopic microsurgery for radical resection of sigmoid cancer is worthy of clinical promotion despite its high technical requirements for the surgeon and certain degree of promotion difficulty, since it boasts high effective rate, low rate of complications, and the contribution for decreased recurrence rate and improved survival. Key words: anal endoscopic microsurgery, sigmoid cancer, effectiveness, safety analysis.