The roles of OGT and its mechanisms in cancer.

O-linked-N-acetylglucosaminylation (O-GlcNAcylation) is a common and important post-translational modification (PTM) linking O-linked ß-N-acetylglucosamine (O-GlcNAc) to serine and threonine residues in proteins. Extensive research indicates its impact on target protein stability, activity, and interactions. O-linked N-acetylglucosamine transferase (OGT) is a critical enzyme that catalyzes O-GlcNAc modification, responsible for adding O-GlcNAc to proteins. OGT and O-GlcNAcylation are overexpressed in many tumors and closely associated with tumor growth, invasion, metabolism, drug resistance, and immune evasion. This review delineates the biochemical functions of OGT and summarizes its effects and mechanisms in tumors. Targeting OGT presents a promising novel approach for treating human malignancies.

Cell-penetrating peptides TAT and 8R functionalize P22 virus-like particles to enhance tissue distribution and retention in vivo.

Virus-like particles (VLPs) are used as nanocontainers for targeted drug, protein, and vaccine delivery. The phage P22 VLP is an ideal macromolecule delivery vehicle, as it has a large exterior surface area, which facilitates multivalent genetic and chemical modifications for cell recognition and penetration. Arginine-rich cell-penetrating peptides (CPPs) can increase cargo transport efficiency in vivo. However, studies on the tissue distribution and retention of P22 VLPs mediated by TAT and 8R are lacking. This study aimed to analyze the TAT and 8R effects on the P22 VLPs transport efficiency and tissue distribution both in vitro and in vivo. We used a prokaryotic system to prepare P22 VLP self-assembled particles and expressed TAT-or 8R-conjugated mCherry on the VLP capsid protein as model cargoes and revealed that the level of P22 VLP-mCherry penetrating the cell membrane was low. However, both TAT and 8R significantly promoted the cellular uptake efficiency of P22 VLPs in vitro, as well as enhanced the tissue accumulation and retention of P22 VLPs in vivo. At 24 h postinjection, TAT enhanced the tissue distribution and retention in the lung, whereas 8R could be better accumulation in brain. Thus, TAT was superior in terms of cellular uptake and tissue accumulation in the P22 VLPs delivery system. Understanding CPP biocompatibility and tissue retention will expand their potential applications in macromolecular cargo delivery.

Effect of postoperative normothermic intraperitoneal chemotherapy on the prognosis of MPM patients receiving CRS+HIPEC: A single-center case-control study.

BACKGROUND: The comprehensive treatment strategy, mainly cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC), combined with systemic and intraperitoneal chemotherapy, is the standard treatment for malignant peritoneal mesothelioma (MPM), which can significantly prolong the survival of patients. The aim of this study is to investigate the clinical significance of postoperative normothermic intraperitoneal chemotherapy (NIPEC) in MPM patients. METHODS: Data of 152 MPM patients who underwent CRS + HIPEC and postoperative intravenous chemotherapy were retrospectively analyzed. Patients were divided into the Non-NIPEC group and the NIPEC group according to whether they received NIPEC after surgery. The baseline characteristics of the two groups were compared, and the survival outcome was analyzed in subgroups according to completeness of cytoreduction (CC) score. Multivariate survival analysis was used to determine the independent prognostic factors. RESULTS: In CC 0-1 and CC 2-3 subgroups, there was no significant difference in baseline characteristics between Non-NIPEC and NIPEC groups. Survival analysis showed that for CC 0-1 patients, there was no significant difference in overall survival (OS) between Non-NIPEC and NIPEC groups (P = 0.503). However, for CC 2-3 patients, the median OS of the NIPEC group was significantly longer than that of the Non-NIPEC group (24.5 vs. 10.3 months, P = 0.005). Pathological type, preoperative thrombosis and postoperative NIPEC (HR = 0.423, 95%CI: 0.228-0.786, P = 0.006) were independent prognostic factors for CC 2-3 patients. CONCLUSIONS: For MPM patients receiving CRS + HIPEC, postoperative intraperitoneal combined with intravenous chemotherapy may improve the survival of CC 2-3 patients, but CC 0-1 patients do not seem to derive the same benefit.

Fine-scale genomic analysis of the tree endophyte Annulohypoxylon sp. FPYF3050 producing monoterpene 1,8-cineole.

1,8-Cineole has a potential in control crop pests and biofuels. The endophytic fungus, Annulohypoxylon sp. FPYF3050 (Neolitsea pulchella), can produce over 90% 1,8-cineole of relative area in its natural volatiles, possessed nematicide properties. The annotated genome of this strain will provide insights into potential application in biofumigation and terpene-based advanced biofuel.

I2-Induced Umpolung: Synthesis of a 1,6-Dihydrofuro[3,2-b]pyrazolo[3,4-e][1,4]thiazine Skeleton via an Unconventional 1,4-Dithiane-2,5-diol Reaction Mode.

In this paper, novel sulfur-containing 1,6-dihydrofuro[3,2-b]pyrazolo[3,4-e][1,4]thiazine skeletons were constructed from the simple and readily available materials enaminone, 5-aminopyrazole, and 1,4-dithiane-2,5-diol. Furthermore, a novel 1,4-dithiane-2,5-diol reaction mode has been developed through a double-dipole-reversal process induced by iodine that results in the formation of six new bonds and two new rings in a one-pot reaction. This method shows good substrate compatibility, and the products can be further modified with a variety of pharmaceuticals. Additionally, this novel skeleton exhibits good fluorescence properties in solution, enabling bright and stable green fluorescence imaging in HeLa cells.

Design, Synthesis, and Biological Evaluation of Covalently Mucoadhesive Derivatives as Nonsystemic Intestine-Targeted TGR5 Agonists.

Takeda G-protein-coupled receptor 5 (TGR5) is considered a promising therapeutic target for treating type 2 diabetes mellitus (T2DM), obesity, and other metabolism-related diseases. Although many TGR5 agonists have been identified, they might cause some side effects in the gallbladder and the heart. To reduce these side effects and improve glucose-lowering capability, we first designed and synthesized a series of 4-phenoxynicotinamide intestine-targeted TGR5 agonist derivatives containing maleimides in the side chains with different linker lengths. All of the target compounds demonstrated significant TGR5 agonistic activity, among which compound 22b displayed the best TGR5 agonistic activity. Additionally, compound 22b displayed low Caco-2 cell permeability and strong mucoadhesion to mucin and the rat intestine. In C57BL/6J, diet-induced obese, and db/db mice, compound 22b demonstrated a robust and prolonged hypoglycemic effect along with an acceptable safety profile.

A retrospective comparative study of robot-assisted unilateral biportal endoscopic lumbar decompression and fusion surgery versus percutaneous endoscopic lumbar decompression and fusion surgery.

The objective of this study is to illustrate the advantages of robot-assisted unilateral biportal endoscopy in lumbar decompression fusion and internal fixation surgery. According to the different surgical methods, we divided the 26 patients into 2 groups, robot-assisted unilateral biportal endoscopy for lumbar interbody fusion (R-ULIF) group and percutaneous endoscopic lumbar decompression and interbody fusion (Endo-LIF) group, with a 1:1 ratio. Gender, disease course, lesion site, fluoroscopy times, operative time, blood loss, postoperative hospital stay, screw placement success rate, fusion rate, complications rate, postoperative pain visual analog scale (VAS) (The VAS score is used only to evaluate pain in the lower back and legs.) Oswestry Disability Index (ODI) (The ODI score can serve as a reference indicator for evaluating the effectiveness of treatment for patients with low back pain, and has good responsiveness in assessing patients with chronic low back pain), and MacNab (The MacNab standard is divided into 4 levels: excellent, good, fair, and poor, which can be used to evaluate the therapeutic efficacy of certain spinal surgeries) standard efficacy evaluation were analyzed and compared between the 2 groups. All patients successfully completed the surgery. Compared with the Endo-LIF group, the R-ULIF group had fewer fluoroscopy procedures, less intraoperative blood loss, and shorter postoperative hospital stay (P < .05). The VAS scores and ODI scores of both groups significantly decreased at all-time points (P < .05). The ODI scores of the R-ULIF group were better than the Endo-LIF group at 1 month and 3 months after surgery (P = .017/P = .047), but there was no statistically significant difference between the groups before surgery and 1 week after surgery (P > .05). The efficacy was evaluated using the MacNab criteria at 6 months after surgery. The R-ULIF group has an excellent and good rate of 84.6%, while the Endo-LIF group has an excellent and good rate of 76.9% (P = 1.000). Robot-assisted unilateral biportal endoscopy for lumbar interbody and fusion surgery has shown short-term clinical efficacy in the treatment of lumbar disc herniation combined with lumbar instability, surpassing endoscopic lumbar interbody fusion surgery. Robot-assisted unilateral biportal endoscopy for lumbar interbody and fusion surgery has demonstrated high success rate in screw placement, minimal radiation exposure, less intraoperative blood loss, shorter hospital stay, and thus deserves further clinical promotion.

Difluorocarbene-Enabled Trifluoromethylation and Cyclization for the Synthesis of 3-(Trifluoromethyl)-4H-pyrans.

A three-component annulation reaction and trifluoromethylation for the construction of 3-(trifluoromethyl)-4H-pyrans using ß-CF3-1,3-enynes, BrCF2CO2Et, and sulfoxonium ylides as readily available substrates has been developed. This metal-free process involves two C-F bond cleavages of ß-CF3-1,3-enynes and a CF3 group generated in situ from BrCF2CO2Et. This method is applicable to the late-stage modification of pharmaceutically active molecules.

Global epidemiological trends in the incidence and deaths of acute respiratory infections from 1990 to 2021.

The aim of this study was to investigate the global epidemiological trends in the incidence and deaths of acute respiratory infections (ARIs), encompassing both upper respiratory infections (URIs) and lower respiratory infections (LRIs), from 1990 to 2021. Using data from the Global Burden of Disease study 2021 (GBD 2021), we utilized the average annual percentage change (AAPC) to examine the trends in the age-standardized incidence rate and deaths rate (ASIR and ASDRs) of URIs and LRIs. In 2021, the global ASIR of URIs and LRIs were 166,770.73 (95 % UI: 148,098.16-189,487.93) per 100,000 and 4283.61 (95 % UI: 4057.03-4524.89) per 100,000, respectively. The highest ASIR of URIs occurred in high-sociodemographic index (SDI) regions (232744.64, 95 % UI: 206887.07-261694.81) per 100,000, whereas LRIs occurred in low-SDI regions (9261.1, 95 % UI: 8741.61-9820.86) per 100,000. In 2021, the global ASDRs of URIs and LRIs were 0.28 (95 % UI: 0.09-0.61) per 100,000 and 28.67 (95 % UI: 25.92-31.07) per 100,000, respectively. The highest ASDRs of both URIs and LRIs were observed in low-SDI regions, with 1.1 (95 % UI: 0.08-2.78) per 100,000 and 70.68 (95 % UI: 62.56-78.62) per 100,000, respectively. From 1990 to 2021, the global ASIR for URIs and LRIs decreased, with AAPCs of -0.17 % (95 % CI: 0.17 % to -0.16 %) and -1.28 % (95 % CI: -1.37 % to -1.22 %), respectively. The global ASDRs also decreased (-3.39 % for URIs; -2.46 % for LRIs). However, during the COVID-19 pandemic, the ASIR of URIs increased in many countries, especially in high-SDI regions (rate difference before and during the COVID-19 pandemic in ASIR was 2210.19 per 100,000.) and low-SDI regions (rate difference in ASIR: 111.26 per 100,000). The global incidence and deaths related to ARIs have decreased over the past 32 years. However, it remains a significant public health concern, particularly due to the notable incidence of URIs in high SDI regions and the deaths associated with both URIs and LRIs in low SDI regions. Furthermore, an increase in the incidence of URIs was observed in both high- and low-SDI regions during the COVID-19 pandemic, highlighting the need for increased attention.

Potential prognostic biomarker SERPINA12: implications for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) remains one of the most prevalent malignant tumors, exhibiting a high morbidity and mortality rate. The mechanism of its occurrence and development requires further study. The objective of this study was to investigate the role of SERPINA12 in the diagnosis, prognosis prediction and biological function within HCC. METHODS: The Cancer Genome Atlas (TCGA) data were employed to analyze the relationship between clinical features and SERPINA12 expression in HCC. Kaplan-Meier curves were utilized to analyze the correlation between SERPINA12 expression and prognosis in HCC. The function of SERPINA12 was determined by enrichment analysis, and the relationship between SERPINA12 expression and immune cell infiltration was investigated. The expression of SERPINA12 was examined in 75 patients with HCC using RT-qPCR and immunohistochemistry, and survival analysis was performed. RESULTS: The expression of SERPINA12 from TCGA database was found to be significantly higher in HCC tissues than in normal tissues and carried a poor prognosis. ROC curve demonstrated the diagnostic potential of SERPINA12 for HCC. The multivariate Cox regression analysis showed that pathologic T stage, tumor status, and SERPINA12 expression were independently associated with patient survival. The SERPINA12 expression was found to correlate with immune cell infiltration. Our RT-qPCR and immunohistochemical analysis revealed high expression of SERPINA12 in tumor tissues. Survival analysis indicated its association with poor prognosis. CONCLUSION: SERPINA12 is a promising biomarker for diagnosis and prognosis, and it is associated with immune cell infiltration.

Ultrasound attenuation imaging as a strategy for evaluation of early and late ambulatory functions in Duchenne muscular dystrophy.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disorder that leads to mobility loss and life-threatening cardiac or respiratory complications. Quantitative ultrasound (QUS) envelope statistics imaging, which characterizes fat infiltration and fibrosis in muscles, has been extensively used for DMD evaluations. PURPOSE: Notably, changes in muscle microstructures also result in acoustic attenuation, potentially serving as another crucial imaging biomarker for DMD. Expanding upon the reference frequency method (RFM), this study contributes to the field by introducing the robust RFM (RRFM) as a novel approach for ultrasound attenuation imaging in DMD. METHODS: The RRFM algorithm was developed using an iterative reweighted least squares technique. We conducted standard phantom measurements with a clinical ultrasound system equipped with a linear array transducer to assess the improvement in attenuation estimation bias by RRFM. Additionally, 161 DMD patients, included in both a validation dataset (n = 130) and a testing dataset (n = 31), underwent ultrasound scanning of the gastrocnemius for RRFM-based attenuation imaging. The diagnostic performances for ambulatory functions and discrimination between early and late ambulatory stages were evaluated and compared with those of QUS envelope statistics imaging (involving Nakagami distribution, homodyned K distribution, and entropy values) using the area under the receiver operating characteristic curve (AUROC). RESULTS: The results indicated that the RRFM method more closely matched the actual attenuation properties of the phantom, reducing measurement bias by 50% compared to conventional RFM. The AUROCs for RRFM-based attenuation imaging, used to discriminate between early and late ambulatory stages, were 0.88 and 0.92 for the validation and testing datasets, respectively. These performances significantly surpassed those of QUS envelope statistics imaging (p < 0.05). CONCLUSIONS: Ultrasound attenuation imaging employing RRFM may serve as a sensitive tool for evaluating the progression of ambulatory function deterioration, offering substantial potential for the health management and follow-up care of DMD patients.

Generation of an infectious cDNA clone for NADC30-like PRRSV.

The porcine reproductive and respiratory syndrome virus (PRRSV) is a highly significant infectious disease that poses a substantial threat to the global pig industry. In recent years, the NADC30-like strain has gradually emerged as prevalent in China, causing a profound impact on the country's pig farming industry. Therefore, it is important to conduct an in-depth study on the characteristics and gene functions of the NADC30-like strain. An infectious cDNA clone is an indispensable tool for investigating the functions of viral genes. In this current study, we successfully isolated a NADC30-like strain and constructed its full-length infectious cDNA clone. The utilization of this clone will facilitate our investigation into the viral replication, pathogenesis, and immune response associated with the PRRSV NADC30-like strain.

Current and future research directions in cellular metabolism of colorectal cancer: A bibliometric analysis.

The primary aim of this study was to analyze the evolving trends and key focal points in research on cellular metabolism of colorectal cancer (CRC). Relevant publications on cellular metabolism in CRC were sourced from the Science Citation Index Expanded within the Web of Science Core Collection database. Bibliometric analysis and visualization were conducted using VOSviewer (version 1.6.18) software and CiteSpace 6.1.R6 (64-bit) Basic. A comprehensive compilation of 4722 English-language publications, covering the period from January 1, 1991 to December 31, 2022, was carefully identified and included in the analysis. Among the authors, "Ogino, Shuji" contributed the most publications in this field, while "Giovannucci, E" garnered the highest number of citations. The journal "Cancer Research" ranked first in both publication volume and citations. Institutionally, "Shanghai Jiao Tong University" emerged as the top contributor in terms of published articles, while "Harvard University" led in citation impact. In country-based analysis, the United States held the top position in both publication output and citations, closely followed by China. The increasing recognition of the significance of cellular metabolism in CRC underscores its potential for novel therapeutic approaches aimed at improving CRC management and prognosis.

Drug sensitivity tumor cell clusters in malignant peritoneal mesothelioma.

BACKGROUND: To explore the most effective adjuvant chemotherapy regimen for malignant peritoneal mesothelioma (MPM) through patient derived tumor-like cell clusters (PTC) drug sensitivity test. METHODS: PTC were cultured in vitro with intraoperative specimens, and drug sensitivity test was performed to calculate the most effective chemotherapy regimen for MPM. The patients were divided into conventional and individualized chemotherapy group according to whether they received PTC drug testing. Univariate and multivariate analyses were conducted to identify independent prognostic factors. RESULTS: Among 186 MPM patients included, 63 underwent PTC culture and drug sensitivity test. The results showed that the most effective chemotherapy regimen was oxaliplatin + gemcitabine. After propensity score matching, a total of 64 patients were enrolled in the following study, including 32 patients receiving individualized chemotherapy guided by PTC drug results as group 1 and 32 patients receiving conventional chemotherapy as group 2. Survival analysis showed that the median OS of group 1 was not reached, significantly longer than that of group 2 (23.5 months) (p < 0.05). CONCLUSIONS: Compared with conventional chemotherapy, individualized chemotherapy guided by PTC drug sensitivity tests can prolong patient survival, and oxaliplatin + gemcitabine + apatinib could be the optimal adjuvant treatment regimen for MPM.

[Recent advances in the bioproduction of mannitol].

D-mannitol is a six-carbon sugar alcohol and one of the most abundant polyols in the nature. With antioxidant and osmotic pressure-regulating effects and non-metabolism by the human body, D-mannitol has been widely used in functional food and pharmaceutical industries. At present, a major way for industrial production of D-mannitol is chemical hydrogenation. In addition, D-Mannitol can be produced by microbial metabolism or catalysis. Compared with the chemical hydrogenation, the microbial methods for synthesizing mannitol do not produce sorbitol as a by-product and have the advantages of mild reaction conditions, strong specificity, and high conversion rate. Microbial fermentation is praised for easy access of strains and raw materials and simple separation of the product. Microbial catalysis usually adopts a multi-enzyme coupling strategy, which uses enzymes produced by engineered bacteria for whole-cell catalysis, and the cofactor recycling pathway is introduced to replenish expensive cofactor. This method can achieve high yields with cheap substrates under mild conditions without the formation of by-products. However, the application of microbial methods in the industrial production of D-mannitol is limited by the high costs of fermentation media and substrates and the long reaction time. This article reviews the reported microbial methods for producing D-mannitol, including the use of high-yielding strains and their fermentation processes, the utilization of low-cost substrates, whole-cell catalytic strategies, and the process control for high productivity. The biosynthesis of mannitol is not only of great significance for promoting industrial upgrading and realizing green manufacturing, but also provides strong support for the development of new bio-based products to meet the growing market demand. With the continuous improvement of technological innovation and industrial chain, it is expected to become one of the main ways of mannitol production in the future.

Divergent synthesis of pyrrolidone fused pyrimido[1,2-b]indazole through selective trapping of an enone intermediate by 1H-indazol-3-amine.

An oxidant-controlled divergent synthesis of a pyrrolidone fused pyrimido[1,2-b]indazole skeleton was developed through selective cyclization of an in situ generated enone intermediate and 1H-indazol-3-amine. The one-pot, metal-free process formed three C-N bonds, one C-C bond, and a tetrasubstituted carbon stereocenter containing a hydroxyl group. This method not only allowed for the synthesis of over 60 new pyrrolidone fused pyrimido[1,2-b]indazole derivatives, but was also compatible with the transformation of complex active molecules and the derivation of target products. Significantly, product 4q exhibited aggregation-induced emission (AIE) characteristics without any further modification.

Radioactive sources search method based on multi-robot and Voronoi partition.

In this paper, it is proposed to locate multiple unknown radioactive sources within a certain time limit through particle filtering and Voronoi partitioning. Firstly, with each robot as a Voronoi centroid, the entire area is partitioned. Then, the robots conduct source search concurrently through particle filtering. When all the robots complete the process of one-particle filtering, the iteration ends and the next one begins until the search for the radioactive source is terminated. Finally, experiment is conducted to demonstrate the efficiency and accuracy of the proposed method.

Similar usage of T-cell receptor ß-chain between tumor and adjacent normal tissue in hepatocellular carcinoma.

BACKGROUND: In this study, we comprehensively profiled the T-cell receptor (TCR) repertoire of the tumor and adjacent normal tissue in patients with HBV-associated hepatocellular carcinoma (HCC) and determined the baseline characteristics and clinical significance of TCR. METHODS: High-throughput sequencing was used to determine the profile of complementarity-determining region 3 (CDR3) of the TCR-ß chain variable (TRBV) in the tumor and normal tissue samples of 14 HCC patients. At the same time, TRBV diversity and differences in expression between tumor and normal tissues were investigated. The cumulative frequency of top 100 CDR3 (CF100), clonality, and Shannon entropy as indices to evaluate diversity, RESULTS: The diversity of TRBV CDR3 showed no significant difference between tumor and normal tissues. Of the 58 V gene segments in TRBV, TRBV16 and TRBV7-6 had a significantly higher frequency in the tumor group than in the normal group (p < 0.05). The frequency of 14 J gene segments showed no significant difference between tumor and normal tissues. In contrast, the frequency of 22 TRBVx/BJx combinations was significantly higher in the tumor than in the normal tissue. In addition, the length and type of TRBV CDR3 were similar in tumor and normal tissues, and a Gaussian distribution was observed in both groups. CONCLUSION: This study provided a large amount of information about the TCR lineage in HBV-associated HCC, laying the foundation for further research. In addition, the fact that the immune repertoire (TRBV CDR3) hardly differs between tumor and adjacent normal tissue provides a new clue for exploring the mechanism of the liver as an organ with immune privileges.

Recommendations for articles and reviews in colorectal cancer-related research at the year-end of 2023.

As peer reviewers of the World Journal of Gastroenterology, our weekly routine involves immersing ourselves in the newly published issue, particularly focusing on the realm of colorectal cancer (CRC) research. We diligently sift through various contributions, ranging from comprehensive reviews to original articles and other scholarly works. Through meticulous examination, we discern the most notable papers, delving into each with careful scrutiny to distill their merits and shortcomings. Undoubtedly, this undertaking demands considerable time and effort. Yet, it stands as an indispensable pursuit, affording us a profound comprehension of the latest breakthroughs in CRC research. Moreover, these meticulously curated selections furnish readers with invaluable resources, serving as enduring references for the nuanced exploration of this dynamic field.

Activation of the G Protein-Coupled Bile Acid Receptor TGR5 Modulates the HCP5/miR-139-5p/DDIT4 Axis to Antagonize Cervical Cancer Progression.

A growing body of evidence indicates that the G protein-coupled bile acid receptor, TGR5, plays a critical role in multiple physiological processes ranging from metabolic disorders to cancers. However, the biological functions of TGR5 in cervical cancer (CC) have not been elucidated. Here, using TGR5 knockout mice, we found that a deficiency of TGR5 leads to greater sensitivity to the progression of cervical inflammation. Activation of TGR5 by its specific ligands significantly attenuated the malignant behavior of CC cells. In addition, we found that TGR5 can negatively modulate the expression of lncRNA HCP5 by blocking its transcription activation when mediated by p65. HCP5 was highly expressed in CC tissues, which was positively correlated with the poor prognosis of CC patients. HCP5 knockdown notably restrained CC cell proliferation, colony formation, and migration in vitro, and inhibited tumor growth in vivo. Furthermore, HCP5 can function as the molecular sponge for miR-139-5p to upregulate DNA damage-induced transcript 4 (DDIT4) in CC cells. Murine xenograft studies demonstrated that TGR5 suppressed the tumor formation of CC cells and downregulated HCP5 and DDIT4 while increasing miR-139-5p in the xenografts. Taken together, these findings, for the first time, indicate that TGR5 inhibits CC progression by regulating the HCP5/miR-139-5p/DDIT4 axis, suggesting that it may represent a novel and potent target for CC treatment.