TGF-ß Promotes Hepatocellular Carcinoma Metastasis Through Through m6A Modification of PCDHGA9.

Objective: Hepatocellular carcinoma (HCC) is a highly lethal cancer with significant mortality, primarily attributed to metastasis. Although Protocadherin Gamma Subfamily A, 9 (PCDHGA9) has been identified as a tumor suppressor gene in cancer metastasis, its role in HCC remains ambiguous. This study aims to clarify the role of PCDHGA9 in HCC by examining its expression, clinical significance, and molecular activities. Methods: Tissue microarray immunofluorescence analysis evaluated the expression of PCDHGA9 and its clinical relevance. In vitro experiments involved manipulating PCDHGA9 levels in SK-HEP-1 cells to assess migration through wound-healing and transwell assays. In vivo, shPCDHGA9 cell injections were utilized to observe effects on tumor growth and metastasis. Protein analysis and Western Blot validated epithelial-mesenchymal transition (EMT)-related proteins. Subsequent to TGF-ß treatment, cell proliferation and apoptosis were quantified using Cell counting kit-8 and flow cytometry, respectively, followed by investigation of TGF-ß effects on PCDHGA9 N6-methyladenosine (m6A) modification via Methylated RNA immunoprecipitation, RT-qPCR, and Western blot analysis. Results: Downregulation of PCDHGA9 expression in HCC tissues is correlated with poor prognosis. In vitro experiments demonstrated that modulating PCDHGA9 expression influenced HCC cell migration. In vivo, PCDHGA9 knockdown is correlated with increased metastasis. Furthermore, TGF-ß stimulation promoted cell proliferation and inhibited apoptosis. Mechanistically, TGF-ß-mediated m6A modification led to PCDHGA9 decay, promoting EMT in HCC cells. Conclusion: PCDHGA9 serves as a potential tumor suppressor in HCC by inhibiting EMT. During this process, TGF-ß is observed to exert regulatory control over m6A modifications of PCDHGA9.

Study of the Structure and Bioactivity of Polysaccharides from Different Parts of Stemona tuberosa Lour.

The polysaccharides from Stemona tuberosa Lour, a kind of plant used in Chinese herbal medicine, have various pharmacological activities, such as anti-inflammatory and antioxidant properties. However, the effects of the extraction methods and the activity of polysaccharides from different parts are still unknown. Therefore, this study aimed to evaluate the effects of different extraction methods on the yields, chemical compositions, and bioactivity of polysaccharides extracted from different parts of Stemona tuberosa Lour. Six polysaccharides were extracted from the leaves, roots, and stems of Stemona tuberosa Lour through the use of hot water (i.e., SPS-L1, SPS-R1, and SPS-S1) and an ultrasound-assisted method (i.e., SPS-L2, SPS-R2, and SPS-S2). The results showed that the physicochemical properties, structural properties, and biological activity of the polysaccharides varied with the extraction methods and parts. SPS-R1 and SPS-R2 had higher extraction yields and total sugar contents than those of the other SPSs (SPS-L1, SPS-L2, SPS-S1, and SPS-S2). SPS-L1 had favorable antioxidant activity and the ability to downregulate MUC5AC expression. An investigation of the anti-inflammatory properties showed that SPS-R1 and SPS-R2 had greater anti-inflammatory activities, while SPS-R2 demonstrated the strongest anti-inflammatory potential. The results of this study indicated that SPS-L1 and SPS-L2, which were extracted from non-medicinal parts, may serve as potent natural antioxidants, but further study is necessary to explore their potential applications in the treatment of diseases. The positive anti-inflammatory effects of SPS-R1 and SPS-R2 in the roots may be further exploited in drugs for the treatment of inflammation.

Hspb1 protects against severe acute pancreatitis by attenuating apoptosis and ferroptosis via interacting with Anxa2 to restore the antioxidative activity of Prdx1.

Acute pancreatitis (AP) is a common abdominal disease that typically resolves on its own, but the mortality rate dramatically increases when it progresses to severe acute pancreatitis (SAP). In this study, we investigated the molecular mechanism underlying the development of SAP from AP. We utilized two SAP models induced by pancreatic duct ligation and caerulein administration. Transcriptomic and proteomic analyses were subsequently performed to determine the mRNA and protein expression profiles of pancreatic samples from SAP and AP model and normal mice. To explore the role of Hspb1 in SAP, we used Hspb1 knockout (KO) mice, a genetically engineered chronic pancreatitis strain (T7D23A), Anxa2 KO mice, and acinar cell-specific Prdx1 knockout mice. Additionally, various in vivo and in vitro assays were performed to elucidate the molecular events and direct targets of Hspb1 in acinar cells. We found that Hspb1 expression was upregulated in AP samples but significantly reduced in acinar cells from SAP samples. KO or inhibition of Hspb1 worsened AP, while AAV8-Hspb1 administration mitigated the severity of SAP and reduced remote organ damage in mice. Furthermore, AAV8-Hspb1 treatment prevented the development of chronic pancreatitis. We found that KO or inhibition of Hspb1 promoted acinar cell death through apoptosis and ferroptosis but not necroptosis or autophagy by increasing reactive oxygen species (ROS) and lipid ROS levels. Mechanistically, Hspb1 directly interacted with Anxa2 to decrease its aggregation and phosphorylation, interact with the crucial antioxidant enzyme Prdx1, and maintain its antioxidative activity by decreasing Thr-90 phosphorylation. Notably, the overexpression of Hspb1 did not have a protective effect on acinar-specific Prdx1 knockout mice. In summary, our findings shed light on the role of Hspb1 in acinar cells. We showed that targeting Hspb1/Anxa2/Prdx1 could serve as a potential therapeutic strategy for SAP.

Comparison of Short-term and Three-year Oncological Outcomes Between Robotic and Laparoscopic Gastrectomy for Gastric Cancer: A Large Multicenter Cohort Study.

OBJECTIVE: To compare the short-term and long-term outcomes between robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for gastric cancer. BACKGROUND: The clinical outcomes of RG over LG have not yet been effectively demonstrated. METHODS: This retrospective cohort study included 3599 patients with gastric cancer who underwent radical gastrectomy at eight high-volume hospitals in China from January 2015 to June 2019. Propensity score matching was performed between patients who received RG and LG. The primary end point was 3-year disease-free survival (DFS). RESULTS: After 1:1 propensity score matching, 1034 pairs of patients were enrolled in a balanced cohort for further analysis. The 3-year DFS in the RG and LG was 83.7% and 83.1% ( P =0.745), respectively, and the 3-year overall survival was 85.2% and 84.4%, respectively ( P =0.647). During 3 years of follow-up, 154 patients in the RG and LG groups relapsed (cumulative incidence of recurrence: 15.0% vs 15.0%, P =0.988). There was no significant difference in the recurrence sites between the 2 groups (all P >0.05). Sensitivity analysis showed that RG had comparable 3-year DFS (77.4% vs 76.7%, P =0.745) and overall survival (79.7% vs 78.4%, P =0.577) to LG in patients with advanced (pathologic T2-4a) disease, and the recurrence pattern within 3 years was also similar between the 2 groups (all P >0.05). RG had less intraoperative blood loss, lower conversion rate, and shorter hospital stays than LG (all P >0.05). CONCLUSIONS: For resectable gastric cancer, including advanced cases, RG is a safe approach with comparable 3-year oncological outcomes to LG when performed by experienced surgeons.

Research progress on phosphatidylinositol 4-kinase inhibitors.

Phosphatidylinositol 4-kinases (PI4Ks) could phosphorylate phosphatidylinositol (PI) to produce phosphatidylinositol 4-phosphate (PI4P) and maintain its metabolic balance and location. PI4P, the most abundant monophosphate inositol in eukaryotic cells, is a precursor of higher phosphoinositols and an essential substrate for the PLC/PKC and PI3K/Akt signaling pathways. PI4Ks regulate vesicle transport, signal transduction, cytokinesis, and cell unity, and are involved in various physiological and pathological processes, including infection and growth of parasites such as Plasmodium and Cryptosporidium, replication and survival of RNA viruses, and the development of tumors and nervous system diseases. The development of novel drugs targeting PI4Ks and PI4P has been the focus of the research and clinical application of drugs, especially in recent years. In particular, PI4K inhibitors have made great progress in the treatment of malaria and cryptosporidiosis. We describe the biological characteristics of PI4Ks; summarize the physiological functions and effector proteins of PI4P; and analyze the structural basis of selective PI4K inhibitors for the treatment of human diseases in this review. Herein, this review mainly summarizes the developments in the structure and enzyme activity of PI4K inhibitors.

Flammulina velutipes polysaccharides regulate lipid metabolism disorders in HFD-fed mice via bile acids metabolism.

Our recent study demonstrated that the dynamic changes of gut microbiota mediated by Flammulina velutipes polysaccharide (FVP) could effectively regulate the lipid metabolism in high fat diet-fed (HFD-fed) obese mice model. In this paper, further research was carried out by examining the bile acid (BAs) profiles, as well as the BAs metabolic pathways changes in obese mice. Furthermore, the regulatory effect of BAs on lipid metabolism was verified by 3 T3-L1 preadipocyte differentiation model. The FVP administration resulted in lower BAs content in plasma of obese mice. From the qRT-PCR analysis, FVP could relieve cholestasis in obese mice through altering the BAs metabolic pathways, changing the related genes expressions in mice liver and ileum. The cholic acid (CA), chenodeoxycholic acid (CDCA), hyodeoxycholic acid (HDCA) and ursodeoxycholic acid (UDCA) were selected in cell experiment which all reduced the intracellular triglyceride content and increased the expression of AMPKα1 in 3 T3-L1 adipocytes. Furthermore, CA and CDCA were found increased the expression of PPARα. In combination with our previous research, we further confirmed in this paper that the changes of BAs metabolism caused by FVP showed a positive effect on lipid metabolism, both in obese mice and 3 T3-L1 adipocytes.

Design, synthesis and anti-inflammatory activity study of lansiumamide analogues for treatment of acute lung injury.

Acute lung injury (ALI) is an inflammation-mediated respiratory disease with a high mortality rate. Medications with anti-inflammatory small molecules have been demonstrated in phase I and II clinical trials to considerably reduce the ALI mortality. In this study, two series of lansiumamide analogues were designed, synthesized, and evaluated for anti-inflammatory activity for ALI treatment. We found that compound 8n exhibited the best anti-inflammatory activity through inhibiting LPS-induced expression of the proinflammatory cytokines interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) in Raw264.7 cells and activating the Nrf2/HO-1 pathway. Furthermore, we discovered in a LPS-induced ALI mice model that compound 8n significantly reduced the infiltration of inflammatory cells into lung tissue to achieve the effect of protecting lung tissues and improving ALI. Additionally, our mice model study revealed that compound 8n had a good expectorant effect. These results consistently support that lansiumamide analogue 8n represents a new class of anti-inflammatory agents with potential as a lead compound for further development into a therapeutic drug for ALI treatment.

The anoikis-related gene signature predicts survival accurately in colon adenocarcinoma.

Colon adenocarcinoma (COAD) is a serious public health problem, the third most common cancer and the second most deadly cancer in the world. About 9.4% of cancer-related deaths in 2020 were due to COAD. Anoikis is a specialized form of programmed cell death that plays an important role in tumor invasion and metastasis. The presence of anti-anoikis factors is associated with tumor aggressiveness and drug resistance. Various bioinformatic methods, such as differential expression analysis, and functional annotation analysis, machine learning, were used in this study. RNA-sequencing and clinical data from COAD patients were obtained from the Gene expression omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Construction of a prognostic nomogram for predicting overall survival (OS) using multivariate analysis and Lasso-Cox regression. Immunohistochemistry (IHC) was our method of validating the expression of seven genes that are linked to anoikis in COAD. We identified seven anoikis-related genes as predictors of COAD survival and prognosis, and confirmed their accuracy in predicting colon adenocarcinoma prognosis by KM survival curves and ROC curves. A seven-gene risk score consisting of NAT1, CDC25C, ATP2A3, MMP3, EEF1A2, PBK, and TIMP1 showed strong prognostic value. Meanwhile, we made a nomogram to predict the survival rate of COAD patients. The immune infiltration assay showed T cells. CD4 memory. Rest and macrophages. M0 has a higher proportion in COAD, and 11 genes related to tumor immunity are important. GDSC2-based drug susceptibility analysis showed that 6 out of 198 drugs were significant in COAD. Anoikis-related genes have potential value in predicting the prognosis of COAD and provide clues for developing new therapeutic strategies for COAD. Immune infiltration and drug susceptibility results provide important clues for finding new personalized treatment options for COAD. These findings also suggest possible mechanisms that may affect prognosis. These results are the starting point for planning individualized treatment and managing patient outcomes.

Carboxymethyl Chitosan/Sodium Alginate/Chitosan Quaternary Ammonium Salt Composite Hydrogel Supported 3J for the Treatment of Oral Ulcer.

Oral ulcer is a common inflammatory disease of oral mucosa, causing severe burning pain and great inconvenience to daily life. In this study, compound 3J with anti-inflammatory activity was synthesized beforehand. Following that, an intelligent composite hydrogel supported 3J was designed with sodium alginate, carboxymethyl chitosan, and chitosan quaternary ammonium salt as the skeleton, and its therapeutic effect on the rat oral ulcer model was investigated. The results show that the composite hydrogel has a dense honeycomb structure, which is conducive to drug loading and wound ventilation, and has biodegradability. It has certain antibacterial effects and good anti-inflammatory activity. When loaded with 3J, it reduced levels of TNF-α and IL-6 in inflammatory cells by up to 50.0%. It has excellent swelling and water retention properties, with a swelling rate of up to 765.0% in a pH 8.5 environment. The existence of a large number of quaternary ammonium groups, carboxyl groups, and hydroxyl groups makes it show obvious differences in swelling in different pH environments, which proves that it has double pH sensitivity. It is beneficial to adapt to the highly dynamic changes of the oral environment. Compared with single hydrogel or drug treatment, the drug-loaded hydrogel has a better effect on the treatment of oral ulcers.

A bioinformatics approach to identify a disulfidptosis-related gene signature for prognostic implication in colon adenocarcinoma.

Colon adenocarcinoma (COAD) is a type of cancer that arises from the glandular epithelial cells that produce mucus in the colon. COAD is influenced by various factors, including genetics, environment and lifestyle. The outcome of COAD is determined by the tumor stage, location, molecular characteristics and treatment. Disulfidptosis is a new mode of cell death that may affect cancer development. We discovered genes associated with disulfidptosis in colon adenocarcinoma and proposed them as novel biomarkers and therapeutic targets for COAD. We analyzed the mRNA expression data and clinical information of COAD patients from The Cancer Genome Atlas (TCGA) database and Xena databases, extracted disulfidptosis-related genes from the latest reports on disulfidptosis. We used machine learning to select key features and build a signature and validated the risk model using data from the Gene Expression Omnibus (GEO) database and Human Protein Atlas (HPA). We also explored the potential biological functions and therapeutic implications of the disulfidptosis-related genes using CIBERSORTx and GDSC2 databases. We identified four disulfidptosis-related genes: TRIP6, OXSM, MYH3 and MYH4. These genes predicted COAD patient survival and modulated the tumor microenvironment, drug sensitivity and immune microenvironment. Our study reveals the importance of disulfidptosis-related genes for COAD prognosis and therapy. Immune infiltration and drug susceptibility results provide important clues for finding new personalized treatment options for COAD. These findings may facilitate personalized cancer treatment.

Heparanase Contributes to Psoriatic Lesions Through Crosstalk with IL-17 Pathway.

Psoriasis is a chronic inflammatory disease that is considered by a network of immunocytes and cytokines. Among all, Th17 cells-derived IL-17 is a critical driving factor in the pathogenesis of psoriasis. Recently, disruption of the extracellular matrix was found to be related to psoriasis progression. In the present study, we aimed to investigate the role of heparanase (HPSE) in psoriasis and the crosstalk with the IL-17 signalling pathway. Skin tissues from non-affected areas and psoriatic lesion areas before and after 12 weeks of IL-17 monoclonal antibody treatment of 30 psoriasis patients were collected. HaCaT cells were treated with different concentrations of IL-17 antibody, and HPSE in cells and medium were measured with Western blotting assay as well as enzyme-linked immunosorbent assay (ELISA). In the imiquimod (IMQ)-induced psoriasis model, IL-17 protein and mRNA expression levels were measured, and changes in the proportion of Th17 cells were detected via flow cytometry. Our data showed that HPSE is upregulated in lesion tissues isolated from psoriasis patients, and was inhibited by anti-IL-17 treatment. In cutaneous cells and IMQ-induced psoriasis model, IL-17 promoted the synthesis of HPSE. Inversely, HPSE was also found to increase the percentage of Th17 cells derived from CD4+ T cells. Finally, we found that the combined treatments of HPSE inhibitor and IL-17 monoclonal antibody produced therapeutic effects on IMQ-induced psoriasis model. Our findings revealed the new role of HPSE in the pathogenesis of psoriasis and also provided a target for combined treatment of psoriasis.

Plasmodium-Resistant Indole Diterpenoid Biosynthesis Gene Cluster Derived from Aspergillus oryzae Was Activated by Exogenous P450 Gene Ast B.

Synthetic biology is an effective way to activate silent biosynthetic gene clusters. Five new indole diterpenoids (1, 2, 5, 9, and 10), together with 10 known derivatives (3, 4, 6-8, and 11-15) were activated from Aspergillus oryzae transformants by an exogenous P450 gene Ast B and obtained under the guidance of molecular networking. Their planar structures were determined by NMR and HR-ESI-MS. The absolute configuration of compound 1 was determined by single crystal X-ray diffraction, and those of compounds 2, 5 , 9, and 10 were confirmed by comparing the observed ECD with the calculated ECD. HPLC analysis suggested that the BGCs of indole diterpenoids in A. oryzae were activated by exogenous P450 gene Ast B. Compounds 1-4, 7, 8, and 11 displayed strong activity against chloroquine-sensitive plasmodium strain P.f.3D7 with IC50 values ranging from 0.84 to 2.9 µM. It is the first report that indole diterpenoids have potential antimalarial activity. The structure-activity relationship study showed that the linear indole diterpenoids contribute significantly to the antiparasite activity. Molecular docking studies showed that 1 and positive control chloroquine were at the center of the active pocket of PfHsp90, while 11 was far from the active site.

Robotic natural orifice specimen extraction surgery versus conventional robotic resection for patients with colorectal neoplasms.

Background: Laparoscopic natural orifice specimen extraction surgery (NOSES) has been widely used in colorectal neoplasms. However, only a few studies have focused on robotic NOSES. This study compared the short-term clinical outcomes and long-term survival outcomes between robotic NOSES and conventional robotic resection (CRR) groups. Methods: From March 2016 to October 2018, a consecutive of 143 patients who underwent robotic sigmoid and rectal resection at the Department of Gastrointestinal Surgery, The Second Xiangya Hospital, Central South University, were considered for inclusion in this study. Propensity-score matching (PSM) was conducted to account for differences in the baseline characteristics. After PSM, 39 patients were included in the robotic NOSES group, and 39 patients in the CRR group. The baseline characteristics between the two groups were all balanced and comparable. Results: Patients in the NOSES group experienced less intraoperative blood loss (p=0.001), lower requirements for additional analgesia (p=0.020), shorter time to first flatus (p=0.010), and a shorter time to first liquid diet (p=0.003) than the CRR group. The 3-year overall survival rates (NOSES: 92.3% vs. CRR: 89.7% p=1.000) and 3-year disease-free survival rates (NOSES: 82.1% vs. CRR: 84.6% p=0.761) between the two groups were comparable. Conclusion: Robotic natural orifice specimen extraction surgery is a safe and feasible surgery for patients with colorectal neoplasms. Robotic NOSES is associated with better short-term clinical outcomes and similar long-term survival outcomes to conventional robotic resection.

Design, synthesis, and biological evaluation of diaryl heterocyclic derivatives targeting tubulin polymerization with potent anticancer activities.

A series of diaryl heterocyclic analogues were designed and synthesized as tubulin polymerization inhibitors. Among them, compound 6y showed the highest antiproliferative activity against HCT-116 colon cancer cell line with an IC50 values of 2.65 µM. Compound 6y also effectively inhibited tubulin polymerization in vitro (IC50 of 10.9 µM), and induced HCT-116 cell cycle arrest in G2/M phase. In addition, compound 6y exhibited high metabolic stability on human liver microsomes (T1/2 = 106.2 min). Finally, 6y was also effective in suppressing tumor growth in a HCT-116 mouse colon model without apparent toxicity. Collectively, these results suggest that 6y represents a new class of tubulin inhibitors deserving further investigation.

Retraction notice to "Tim-4 promotes the growth of colorectal cancer by activating angiogenesis and recruiting tumor-associated macrophages via the PI3K/AKT/mTOR signaling pathway" [Canc. Lett. 436 (2018) 119-128].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). .

Advances in the development of phosphodiesterase-4 inhibitors.

Phosphodiesterase 4 (PDE4) hydrolyzes cyclic adenosine monophosphate (cAMP) and plays a vital roles in many biological processes. PDE4 inhibitors have been widely studied as therapeutics for the treatment of various diseases, including asthma, chronic obstructive pulmonary disease (COPD) and psoriasis. Many PDE4 inhibitors have progressed to clinical trials and some have been approved as therapeutic drugs. Although many PDE4 inhibitors have been approved to enter clinical trials, however, the development of PDE4 inhibitors for the treatment of COPD or psoriasis has been hampered by their side effects of emesis. Herein, this review summarizes advances in the development of PDE4 inhibitors over the last ten years, focusing on PDE4 sub-family selectivity, dual target drugs, and therapeutic potential. Hopefully, this review will contribute to the development of novel PDE4 inhibitors as potential drugs.

A propensity score matching study of totally robotic right hemicolectomy versus robot-assisted right hemicolectomy.

To compare and analyze the differences in safety, feasibility and short-term efficacy between robot-assisted right hemicolectomy (RARH) and totally robotic right hemicolectomy (TRRH). We collected the information of 184 patients who underwent right hemicolectomy in the Second Xiangya Hospital of Central South University from July 2016 to December 2021. We matched 148 patients (74 with robot-assisted right hemicolectomy and 74 with totally robotic right hemicolectomy) to conduct a retrospective analysis of their clinical outcomes. The incision lengths were 5.14 ± 0.60 cm in the RARH group and 4.74 ± 0.55 cm in the TRRH (p < 0.001). The blood losses were 86.28 ± 52.57 mL in the RARH group and 69.19 ± 44.78 mL in the TRRH (p = 0.035). The operative times were 197.50 min (171.25-242.25) in the RARH group and 160.00 min (145.00-188.75) in the TRRH (p < 0.001). The postoperative hospital stays were 11.18 ± 4.32 days in the RARH group and 9.53 ± 4.42 days in the TRRH (p = 0.023). The NRS pain scores were 3.05 ± 0.23 in the RARH group and 2.96 ± 0.26 in the TRRH (p = 0.019). The abdominal drainage extraction times were 7.54 ± 1.44 days in the RARH group and 7.00 ± 1.25 days in the TRRH (p = 0.016). Postoperative complications in the RARH group are fewer than TRRH (p = 0.033). TRRH is safe and feasible. Compared with RARHs, the TRRHs resulted in shorter incision lengths, operative times, intraoperative blood losses, postoperative hospital stays, first flatus times, first liquid diet times, and drainage tube removal times, and they improved NRS pain scores and postoperative complication frequencies.

Two Green Protocols for Halogenative Semipinacol Rearrangement.

Semipinacol rearrangement is a special type of Wagner-Meerwein rearrangement that involves carbocation 1,2-rearrangement to provide carbonyl compounds with an α-quaternary carbon center. It has been strategically used for natural product synthesis and construction of highly congested quaternary carbons. Herein, we report a safe and green protocol that uses oxone/halide and Fenton bromide to achieve halogenative semipinacol rearrangement. The key feature of this method is the green in situ generation of reactive halogenating species from oxidation of halide with oxone or H2O2, which produces a nontoxic byproduct (potassium sulfate or water). Easy operation (insensitive to air and moisture) at room temperature without using special equipment adds additional advantage over previous methods.

miR-145-5p affects the proliferation of colorectal cancer cells and cytotoxicity of NK cells by targeting regulation of RAD18 expression / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探索RAD18影响结直肠癌细胞增殖及调节NK细胞对结直肠细胞的杀伤作用及其可能的机制。方法：采用生物信息学技术分析结直肠癌组织中RAD18和miR-145-5p的表达及两者之间的调控关系、分析RAD18富集通路。采用qPCR法验证RAD18和miR-145-5p在结直肠癌细胞中的表达，双荧光素酶报告基因实验验证miR-145-5p与RAD18的调控关系。按转染物的不同将SW480、HCT-15细胞分为将si-RAD18组、si-NC组，另向SW480细胞分别转染inhibitor-NC+si-NC、miR-145-5p inhibitor+si-NC或miR-145-5p inhibitor+si-RAD18，采用CCK-8法、克隆形成实验分别检测敲降miR-145-5p和/或RAD18对细胞增殖、克隆形成的影响；将各组细胞分别与经IL-2激活的NK92细胞共培养，采用乳酸脱氢酶释放法、ELISA和免疫荧光染色法分别检测NK细胞的细胞毒性、细胞因子分泌及细胞表面穿孔素和颗粒酶B表达的影响。结果：RAD18在结直肠癌组织和细胞中呈高表达（均P<0.01）。敲降RAD18可以抑制结直肠癌细胞增殖能力（P<0.05）和促进NK细胞活力、细胞毒性、IFN-γ、TNF-α、GM-CSF分泌及穿孔素和颗粒酶B的表达（均P<0.05）。双荧光素酶报告实验验证了RAD18-3’UTR与miR-145-5p的结合关系，miR-145-5p在结直肠癌组织和细胞中低表达（P<0.05或P<0.01）。miR-145-5p可以靶向下调RAD18的表达（P<0.05），过表达RAD18可以逆转miR-145-5p过表达对NK细胞杀伤效应的促进作用（均P<0.05）。结论：miR-145-5p可靶向下调RAD18的表达，miR-145-5p/RAD18轴能够影响结直肠癌细胞的增殖和NK细胞对其的细胞毒作用。