miR-181-5p/KLHL5 Promoted Proliferation and Migration of Gastric Cancer Through Activating METTL3-Mediated m6A Process.

KLHL5 was a member of kelch-repeat protein family and was involved in the initiation of progression of a plethora of cancers. However, its specific role in gastric cancer was not explicitly illustrated. In this context, we aimed to investigate the biological role and mechanisms about KLHL5 in gastric cancer. qRT-PCR and western blot were used to investigate the expression of KLHL5 and EMT biomarkers. Wound healing assay, CCK-8, and Transwell assay were used to investigate the biological function of KLHL5. We found that KLHL5 was highly expressed in gastric cancer both in vivo and in vitro; besides, its high expression led to a shorter overall survival. Following statistical analysis showed that KLHL5 was associated with M stage. As for molecular experiments, we found that KLHL5 knockdown significantly reduced the proliferation, migration, and invasion ability of gastric cancer cell line MKN45 and SGC-7901. Furthermore, we found that miR-181-5p targeted KLHL5 to regulate m6A level through METTL3. In addition, KLHL5 knockdown could significantly reduce the lung metastasis rate in mice. In conclusion, we found that miR-181-5p/KLHL5 could promote the proliferation, migration, and invasion of gastric cancer by activating m6A process through regulating METTL3.

Esophageal magnetic compression anastomosis in dogs.

BACKGROUND: Magnetic compression anastomosis (MCA) is a novel suture-free reconstruction of the digestive tract. It has been used in gastrointestinal anastomosis, jejunal anastomosis, cholangioenteric anastomosis and so on. The traditional operative outcomes of congenital esophageal atresia and benign esophageal stricture are poor, and there are too many complications postoperatively. AIM: To test MCA technology to reconstruct the esophagus in dogs, prior to studying the feasibility and safety of MCA in humans. METHODS: Thirty-six dogs were randomized into either the study or control group (n = 18 per group). The dogs in the study group were subjected to end-to-end esophageal anastomosis with the magnetic compression device, while those in the control group underwent hand-sewn anastomosis with 4-0 absorbable multifilament Vicryl. We used interrupted single-layer inverting sutures. The anastomosis time, gross appearance, weight and pathology of the anastomosis were evaluated at one month, three months and six months postoperatively. RESULTS: The anastomosis time of the MCA group was shorter than that of the hand-sewn group (7.5 ± 1.0 min vs 12.5 ± 1.8 min, P < 0.01). In the MCA group, X-ray examination was performed every day to locate the magnetic device in the esophagus before the magnetic device fell off from the esophagus. In the hand-sewn group, dogs did not undergo X-ray examination. One month after the surgeries, the mean weight of the dogs in the hand-sewn group had decreased more than that of the dogs in the MCA group (11.63 ± 0.71 kg vs 12.73 ± 0.80 kg, P < 0.05). At 3 mo and 6 mo after the operation, the dogs' weights were similar between the two groups (13.75 ± 0.84 kg vs 14.03 ± 0.82 kg, 14.93 ± 0.80 kg vs 15.44 ± 0.47 kg). The number of inflammatory cells in MCA group was lower than that in hand-sewn group on 1 mo after operation. CONCLUSION: MCA is an effective and safe method for esophageal reconstruction. The anastomosis time of the MCA group was less than that of the hand-sewn group. This study shows that MCA technology may be applied to human esophageal reconstruction, provided these favorable results are confirmed by more publications.

Tumor oxygenation nanoliposome synergistic hypoxia-inducible-factor-1 inhibitor enhanced Iodine-125 seed brachytherapy for esophageal cancer.

Iodine-125 (125I) brachytherapy has become one of the most effective palliative treatment options for advanced esophageal cancer. However, resistance toward 125I brachytherapy caused by pre-existing tumor hypoxia and hypoxia-inducible factor 1 (HIF-1) signaling pathway activation represents a significant limitation in esophageal cancer treatment. To circumvent these problems, herein, we proposed an innovative strategy to alleviate radioresistance of brachytherapy by co-encapsulating catalase (CAT) and HIF-1 inhibitor-acriflavine (ACF) into the hydrophilic cavities of liposome, termed as "ACF-CAT@Lipo". Under overexpressed H2O2 stimulation in the tumor region, the fabricated ACF-CAT@Lipo can generate an amount of O2 and alleviate tumor hypoxia in vitro and in vivo. Furthermore, cooperating with ACF, the expression of hypoxia-related protein (e.g. HIF-1α, VEGF, MMP-2) are obviously decreased. Importantly, the copious oxygenation and the significant inhibition expression of HIF-1α can further improve the radiosensitivity of 125I brachytherapy and finally realize the eradication of esophageal cancer in vivo. The oxygen enrichment and HIF-1 inhibition function of ACF-CAT@Lipo provides a new strategy to overcome the brachytherapy resistance of esophageal cancer therapy.