Dual growth factor methacrylic alginate microgels combined with chitosan-based conduits facilitate peripheral nerve repair.

Treating severe peripheral nerve injuries is difficult. Nerve repair with conduit small gap tubulization is a treatment option but still needs to be improved. This study aimed to assess the use of microgels containing growth factors, along with chitosan-based conduits, for repairing nerves. Using the water-oil emulsion technique, microgels of methacrylic alginate (AlgMA) that contained vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) were prepared. The effects on rat Schwann cells (RSC96) and human umbilical vein endothelial cells (HUVECs) were evaluated. Chitosan-based conduits were fabricated and used in conjunction with microgels containing two growth factors to treat complete neurotmesis in rats. The results showed that the utilization of dual growth factor microgels improved the migration and decreased the apoptosis of RSC96 cells while promoting the growth and formation of tubes in HUVECs. The utilization of dual growth factor microgels and chitosan-based conduits resulted in notable advancements in the regeneration and myelination of nerve fibers, recovery of neurons, alleviation of muscle atrophy and recovery of neuromotor function and nerve conduction. In conclusion, the use of dual growth factor AlgMA microgels in combination with chitosan-based conduits has the potential to significantly improve the effectiveness of nerve repair.

The mechanism of adipose mesenchymal stem cells to stabilize the immune microenvironment of pelvic floor injury by regulating pyroptosis and promoting tissue repair.

Pelvic organ prolapse (POP) has a high incidence rate among Chinese women. Repeated mechanical stimulation is an important factor causing POP, but the injury mechanism has not yet been elucidated. The purpose of this study is to explore the related mechanisms of pelvic floor supporting tissue damage caused by mechanical force and the application of stem cell therapy. First, we obtained vaginal wall and sacral ligament tissue samples from clinical patients for examination. Pelvic floor support tissues of POP patients displayed high expression of inflammation and immune disorders. Then, we constructed a rat model of childbirth injury. In vivo and in vitro experiments investigated the key mechanism of pelvic floor support tissue injury caused by mechanical force. We discovered that after mechanical force, a large number of reactive oxygen species (ROS) and macrophages rapidly accumulated in pelvic floor tissues. ROS stimulated macrophages to produce NLRP3 inflammatory complex, induced the release of interleukin (IL-1ß) and pyroptosis and exacerbated the inflammatory state of damaged tissues, persisting chronic inflammation of fibroblasts in supporting tissues, thus causing the pelvic floor's extracellular matrix (ECM) collagen metabolic disorder. Resultingly impeding the repair process, thereby causing the onset and progression of the disease. Through their paracrine ability, we discovered that adipose mesenchymal stem cells (ADSCs) could inhibit this series of pathological processes and promote tissue repair, asserting a good therapeutic effect. Simultaneously, to overcome the low cell survival rate and poor therapeutic effect of directly injecting cells, we developed a ROS-responsive PVA@COLI hydrogel with ADSCs. The ROS-scavenging properties of the gel could reshape the site of inflammation injury, enhance cell survival, and play a role in subsequent treatment. The findings of this study could serve as a basis for early, targeted intervention therapy for POP and representing a promising approach.

Growth factors: Bioactive macromolecular drugs for peripheral nerve injury treatment - Molecular mechanisms and delivery platforms.

Bioactive macromolecular drugs known as Growth Factors (GFs), approved by the Food and Drug Administration (FDA), have found successful application in clinical practice. They hold significant promise for addressing peripheral nerve injuries (PNIs). Peripheral nerve guidance conduits (NGCs) loaded with GFs, in the context of tissue engineering, can ensure sustained and efficient release of these bioactive compounds. This, in turn, maintains a stable, long-term, and effective GF concentration essential for treating damaged peripheral nerves. Peripheral nerve regeneration is a complex process that entails the secretion of various GFs. Following PNI, GFs play a pivotal role in promoting nerve cell growth and survival, axon and myelin sheath regeneration, cell differentiation, and angiogenesis. They also regulate the regenerative microenvironment, stimulate plasticity changes post-nerve injury, and, consequently, expedite nerve structure and function repair. Both exogenous and endogenous GFs, including NGF, BDNF, NT-3, GDNF, IGF-1, bFGF, and VEGF, have been successfully loaded onto NGCs using techniques like physical adsorption, blend doping, chemical covalent binding, and engineered transfection. These approaches have effectively promoted the repair of peripheral nerves. Numerous studies have demonstrated similar tissue functional therapeutic outcomes compared to autologous nerve transplantation. This evidence underscores the substantial clinical application potential of GFs in the domain of peripheral nerve repair. In this article, we provide an overview of GFs in the context of peripheral nerve regeneration and drug delivery systems utilizing NGCs. Looking ahead, commercial materials for peripheral nerve repair hold the potential to facilitate the effective regeneration of damaged peripheral nerves and maintain the functionality of distant target organs through the sustained release of GFs.

Chitosan-Based Conduits with Different Inner Diameters at both Ends Combined with Modified Formula Radix Hedysari Promote Nerve Transposition Repair.

BACKGROUND: Severe peripheral nerve injuries, such as deficits over long distances or proximal nerve trunk injuries, pose complex reconstruction challenges that often result in unfavorable outcomes. An innovative approach to repairing severe peripheral nerve damage involves using conduit suturing for nerve transposition repair. Cylindrical nerve guides are typically unsuitable for nerve transposition repair. Moreover, postsurgical adjuvant treatment is essential to promote the development of axonal lateral sprouts, proximal growth, and the restoration of neurostructure and function. The purpose of this research is to assess the impact of chitosan-based conduits with varying inner diameters on nerve transposition repair when combined with modified formula Radix Hedysari (MFRH). METHODS: Using chitosan, we created conduits with varying inner diameters on both ends. These conduits were then utilized to repair the distal common peroneal and tibial nerves in SD rats using the proximal common peroneal nerve. Subsequently, MFRH was employed as a supplementary treatment. The assessment of the repair's effectiveness took place 16 weeks postsurgery, utilizing a range of techniques, including the neurological nerve function index, neuroelectrophysiological measurements, muscle wet weight, and examination of nerve and muscle histology. RESULTS: The outcomes of our study showed that following 16 weeks of postoperative treatment, MFRH had a significant positive impact on the recovery of neuromotor and nerve conduction abilities. Moreover, there was a significant increase in the ratio of wet weight of muscles, cross-sectional area of muscle fibers, quantity and structure of regenerated myelinated nerve fibers, and the count of neurons. CONCLUSIONS: A combination of chitosan-based chitin conduits possessing different inner diameters and MFRH can considerably promote the regeneration and functional recovery of damaged nerves, which in turn enhances nerve transposition repair efficacy.

Multifunctional wet-adhesive chitosan/acrylic conduit for sutureless repair of peripheral nerve injuries.

The incidence of peripheral nerve injury (PNI) is high worldwide, and a poor prognosis is common. Surgical closure and repair of the affected area are crucial to ensure the effective treatment of peripheral nerve injuries. Despite being the standard treatment approach, reliance on sutures to seal the severed nerve ends introduces several limitations and restrictions. This technique is intricate and time-consuming, and the application of threading and punctate sutures may lead to tissue damage and heightened tension concentrations, thus increasing the risk of fixation failure and local inflammation. This study aimed to develop easily implantable chitosan-based peripheral nerve repair conduits that combine acrylic acid and cleavable N-hydroxysuccinimide to reduce nerve damage during repair. In ex vivo tissue adhesion tests, the conduit achieved maximal interfacial toughness of 705 J m-2 ± 30 J m-2, allowing continuous bridging of the severed nerve ends. Adhesive repair significantly reduces local inflammation caused by conventional sutures, and the positive charge of chitosan disrupts the bacterial cell wall and reduces implant-related infections. This promises to open new avenues for sutureless nerve repair and reliable medical implants.

Chitin Conduits with Different Inner Diameters at Both Ends Combined with Dual Growth Factor Hydrogels Promote Nerve Transposition Repair in Rats.

Severe peripheral nerve injuries, such as deficits over long distances or proximal nerve trunk injuries, pose complex reconstruction challenges that often result in unfavorable outcomes. Innovative techniques, such as nerve transposition repair with conduit suturing, can be employed to successfully treat severe peripheral nerve damage. However, cylindrical nerve guides are typically unsuitable for nerve transposition repair. Furthermore, angiogenic and neurotrophic factors are necessary to stimulate the emergence of axonal lateral sprouts, proximal growth, and the rehabilitation of neuron structures and functions. In the current study, we used chitosan to make chitin conduits with different inner diameters at both ends, combined with gelatin methacrylate hydrogels that can continuously release dual growth factors, namely, the vascular endothelial growth factor (VEGF) and the nerve growth factor (NGF), and evaluated its impact on nerve transposition repair in rats. At 16 weeks after the operation, our findings showed that the conduit combined with the dual growth factor hydrogel significantly improved the restoration of both motor and conduction functions of the nerve. In addition, histological analysis showed significant recovery of nerve fibers, target muscles, and neurons. In conclusion, the combination of chitin conduits with different inner diameters and dual growth factor hydrogels can significantly improve the effect of nerve transposition repair, which has important potential clinical value.

The Porous Structure of Peripheral Nerve Guidance Conduits: Features, Fabrication, and Implications for Peripheral Nerve Regeneration.

Porous structure is an important three-dimensional morphological feature of the peripheral nerve guidance conduit (NGC), which permits the infiltration of cells, nutrients, and molecular signals and the discharge of metabolic waste. Porous structures with precisely customized pore sizes, porosities, and connectivities are being used to construct fully permeable, semi-permeable, and asymmetric peripheral NGCs for the replacement of traditional nerve autografts in the treatment of long-segment peripheral nerve injury. In this review, the features of porous structures and the classification of NGCs based on these characteristics are discussed. Common methods for constructing 3D porous NGCs in current research are described, as well as the pore characteristics and the parameters used to tune the pores. The effects of the porous structure on the physical properties of NGCs, including biodegradation, mechanical performance, and permeability, were analyzed. Pore structure affects the biological behavior of Schwann cells, macrophages, fibroblasts, and vascular endothelial cells during peripheral nerve regeneration. The construction of ideal porous structures is a significant advancement in the regeneration of peripheral nerve tissue engineering materials. The purpose of this review is to generalize, summarize, and analyze methods for the preparation of porous NGCs and their biological functions in promoting peripheral nerve regeneration to guide the development of medical nerve repair materials.

Prospects of Using Chitosan-Based Biopolymers in the Treatment of Peripheral Nerve Injuries.

Peripheral nerve injuries are common neurological disorders, and the available treatment options, such as conservative management and surgical repair, often yield limited results. However, there is growing interest in the potential of using chitosan-based biopolymers as a novel therapeutic approach to treating these injuries. Chitosan-based biopolymers possess unique characteristics, including biocompatibility, biodegradability, and the ability to stimulate cell proliferation, making them highly suitable for repairing nerve defects and promoting nerve regeneration and functional recovery. Furthermore, these biopolymers can be utilized in drug delivery systems to control the release of therapeutic agents and facilitate the growth of nerve cells. This comprehensive review focuses on the latest advancements in utilizing chitosan-based biopolymers for peripheral nerve regeneration. By harnessing the potential of chitosan-based biopolymers, we can pave the way for innovative treatment strategies that significantly improve the outcomes of peripheral nerve injury repair, offering renewed hope and better prospects for patients in need.

Mimosa-Inspired Stimuli-Responsive Curling Bioadhesive Tape Promotes Peripheral Nerve Regeneration.

Trauma often results in peripheral nerve injuries (PNIs). These injuries are particularly challenging therapeutically because of variable nerve diameters, slow axonal regeneration, infection of severed ends, fragility of the nerve tissue, and the intricacy of surgical intervention. Surgical suturing is likely to cause additional damage to peripheral nerves. Therefore, an ideal nerve scaffold should possess good biocompatibility, diameter adaptability, and a stable biological interface for seamless biointegration with tissues. Inspired by the curl of Mimosa pudica, this study aimed to design and develop a diameter-adaptable, suture-free, stimulated curling bioadhesive tape (SCT) hydrogel for repairing PNI. The hydrogel is fabricated from chitosan and acrylic acid-N-hydroxysuccinimide lipid via gradient crosslinking using glutaraldehyde. It closely matches the nerves of different individuals and regions, thereby providing a bionic scaffold for axonal regeneration. In addition, this hydrogel rapidly absorbs tissue fluid from the nerve surface achieving durable wet-interface adhesion. Furthermore, the chitosan-based SCT hydrogel loaded with insulin-like growth factor-I effectively promotes peripheral nerve regeneration with excellent bioactivity. This procedure for peripheral nerve injury repair using the SCT hydrogel is simple and reduces the difficulty and duration of surgery, thereby advancing adaptive biointerfaces and reliable materials for nerve repair.

Proposal and validation of a new classification for trochanteric fractures based on medial buttress and lateral cortical integrity.

Background: Trochanteric fractures usually require surgical treatment. The currently used classification system, such as AO classification, cannot cover all variant types, and is poor in reliability, causing confusion in surgical decision making. This study describes a simple, well-covered, re-liable, accurate, and clinically useful classification. Methods: We retrospectively reviewed the records of 907 patients with trochanteric fractures treated by us from 1,999 to 2019 and proposed a new classification according to radiographs. Then, 50 records randomly selected in proportion were examined by 10 observers (5 experienced and 5 inexperienced) independently according to AO and the new classification. After a 2-week interval, repeat evaluation was completed. The Kappa coefficient was used to investigate the intra-observer reliability, inter-observer reliability and the agreement between the observers and the "reference standard". Results: The new classification system includes 12 types composed of 3 medial groups and 4 lateral groups. According to the medial buttress, the fractures are divided into group I (intact lesser trochanter, adequate but-tress), group II (incomplete lesser trochanter, effective cortical buttress after reduction) and group III (huge defect of the medial cortex). According to the penetration region of the lateral fracture line, the fractures are divided into group A (intact lateral cortex), group B (incomplete lateral cortex), group C (subtrochanteric fractures) and group D (multiple lateral fracture lines). All of the included cases can be classified according to the new classification, of which 34 (3.75%) cases are unclassifiable by the AO classification. Intra-observer: The experienced achieved substantial agreement using both AO [k = 0.61 (95% confidence interval 0.46-0.76)] and new classification [k = 0.65 (0.55-0.76)]. The inexperienced reached moderate agreement using both AO [k = 0.48 (0.33-0.62)] and new classification [k = 0.60 (0.50-0.71)]. Inter-observer: The overall reliabilities for AO [k = 0.51 (0.49-0.53)] and for new classification [k = 0.57 (0.55-0.58)] were both moderate. The agreement between the experienced and the reference standard according to AO [k = 0.61 (0.49-0.74)] and new classification [k = 0.63 (0.54-0.72)] were both substantial. The agreement between the inexperienced and the reference standard according to AO [k = 0.48 (0.45-0.50)] and the new classification [k = 0.48 (0.41-0.54)] were both moderate. Conclusion: Compared with AO classification, our new classification is better in coverage, reliability and accuracy, and has the feasibility of clinical verification and promotion.

An electroencephalography-based human-machine interface combined with contralateral C7 transfer in the treatment of brachial plexus injury.

Transferring the contralateral C7 nerve root to the median or radial nerve has become an important means of repairing brachial plexus nerve injury. However, outcomes have been disappointing. Electroencephalography (EEG)-based human-machine interfaces have achieved promising results in promoting neurological recovery by controlling a distal exoskeleton to perform functional limb exercises early after nerve injury, which maintains target muscle activity and promotes the neurological rehabilitation effect. This review summarizes the progress of research in EEG-based human-machine interface combined with contralateral C7 transfer repair of brachial plexus nerve injury. Nerve transfer may result in loss of nerve function in the donor area, so only nerves with minimal impact on the donor area, such as the C7 nerve, should be selected as the donor. Single tendon transfer does not fully restore optimal joint function, so multiple functions often need to be reestablished simultaneously. Compared with traditional manual rehabilitation, EEG-based human-machine interfaces have the potential to maximize patient initiative and promote nerve regeneration and cortical remodeling, which facilitates neurological recovery. In the early stages of brachial plexus injury treatment, the use of an EEG-based human-machine interface combined with contralateral C7 transfer can facilitate postoperative neurological recovery by making full use of the brain's computational capabilities and actively controlling functional exercise with the aid of external machinery. It can also prevent disuse atrophy of muscles and target organs and maintain neuromuscular junction effectiveness. Promoting cortical remodeling is also particularly important for neurological recovery after contralateral C7 transfer. Future studies are needed to investigate the mechanism by which early movement delays neuromuscular junction damage and promotes cortical remodeling. Understanding this mechanism should help guide the development of neurological rehabilitation strategies for patients with brachial plexus injury.

Application of Chitosan and Its Derivative Polymers in Clinical Medicine and Agriculture.

Chitosan is a biodegradable natural polymer derived from the exoskeleton of crustaceans. Because of its biocompatibility and non-biotoxicity, chitosan is widely used in the fields of medicine and agriculture. With the latest technology and technological progress, different active functional groups can be connected by modification, surface modification, or other configurations with various physical, chemical, and biological properties. These changes can significantly expand the application range and efficacy of chitosan polymers. This paper reviews the different uses of chitosan, such as catheter bridging to repair nerve broken ends, making wound auxiliaries, as tissue engineering repair materials for bone or cartilage, or as carriers for a variety of drugs to expand the volume or slow-release and even show potential in the fight against COVID-19. In addition, it is also discussed that chitosan in agriculture can improve the growth of crops and can be used as an antioxidant coating because its natural antibacterial properties are used alone or in conjunction with a variety of endophytic bacteria and metal ions. Generally speaking, chitosan is a kind of polymer material with excellent development prospects in medicine and agriculture.

Application of Hybrid Electrically Conductive Hydrogels Promotes Peripheral Nerve Regeneration.

Peripheral nerve injury (PNI) occurs frequently, and the prognosis is unsatisfactory. As the gold standard of treatment, autologous nerve grafting has several disadvantages, such as lack of donors and complications. The use of functional biomaterials to simulate the natural microenvironment of the nervous system and the combination of different biomaterials are considered to be encouraging alternative methods for effective tissue regeneration and functional restoration of injured nerves. Considering the inherent presence of an electric field in the nervous system, electrically conductive biomaterials have been used to promote nerve regeneration. Due to their singular physical properties, hydrogels can provide a three-dimensional hydrated network that can be integrated into diverse sizes and shapes and stimulate the natural functions of nerve tissue. Therefore, conductive hydrogels have become the most effective biological material to simulate human nervous tissue's biological and electrical characteristics. The principal merits of conductive hydrogels include their physical properties and their electrical peculiarities sufficient to effectively transmit electrical signals to cells. This review summarizes the recent applications of conductive hydrogels to enhance peripheral nerve regeneration.

XT-type DNA hydrogels loaded with VEGF and NGF promote peripheral nerve regeneration via a biphasic release profile.

Peripheral nerve injury (PNI) remains an unresolved challenge in the medicine area. With the development of biomaterial science and tissue engineering, a variety of nerve conduits were widely applied for repairing long defect PNI. DNA materials are developing rapidly due to their multiple advantages. In the present study, we aim to combine a DNA hydrogel, vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) to construct a new type of delivery system, which could achieve a biphasic release profile of VEGF and NGF by taking advantage of the different degradation rates between X- and T-type DNA. In vitro results showed that the DNA gel + VEGF/NGF system could promote proliferation, migration and myelination of Rat Schwann cells (RSC) while maintaining cell viability. In vivo results indicated a better effect of DNA gel + VEGF/NGF on promoting repair of long defect PNI than the hollow chitin conduits (CT), DNA gel or VEGF/NGF group. The new technology invention holds promising clinical application prospects for repairing PNI and may be used broadly after step-by-step improvement.

Chitin Nerve Conduits with Three-Dimensional Spheroids of Mesenchymal Stem Cells from SD Rats Promote Peripheral Nerve Regeneration.

Peripheral nerve injury (PNI) is an unresolved medical problem with limited therapeutic effects. Epineurium neurorrhaphy is an important method for treating PNI in clinical application, but it is accompanied by inevitable complications such as the misconnection of nerve fibers and neuroma formation. Conduits small gap tubulization has been proved to be an effective suture method to replace the epineurium neurorrhaphy. In this study, we demonstrated a method for constructing peripheral nerve conduits based on the principle of chitosan acetylation. In addition, the micromorphology, mechanical properties and biocompatibility of the chitin nerve conduits formed by chitosan acetylation were further tested. The results showed chitin was a high-quality biological material for constructing nerve conduits. Previous reports have demonstrated that mesenchymal stem cells culture as spheroids can improve the therapeutic potential. In the present study, we used a hanging drop protocol to prepare bone marrow mesenchymal stem cell (BMSCs) spheroids. Meanwhile, spherical stem cells could express higher stemness-related genes. In the PNI rat model with small gap tubulization, BMSCs spheres exhibited a higher ability to improve sciatic nerve regeneration than BMSCs suspension. Chitin nerve conduits with BMSCs spheroids provide a promising therapy option for peripheral nerve regeneration.

Knockdown of COPS3 inhibits the progress of prostate cancer through reducing phosphorylated p38 MAPK expression and impairs the epithelial-mesenchymal transition process.

BACKGROUND: The amplification of gene COPS3 is closely related to the development of osteosarcoma and hepatocellular carcinoma. However, the effects of COPS3 on prostate cancer (PCa) are poorly understood. METHODS: In this study, the protein expression of COPS3 in PCa tissues, adjacent normal tissues, and bone metastasis tissues of PCa was analyzed by immunohistochemistry. Furthermore, cell proliferation, colony formation, migration, and invasion assay were performed in 22rv1 and PC-3 cells after knocking down COPS3 by small interfering RNAs. Furthermore, we performed western blot analysis to explore the potential mechanisms underlying it. RESULTS: This study found that the overall survival of the COPS3 high-expression group was significantly shorter than the low-expression group. This study discovered that the protein expression of COPS3 in PCa tissues was higher than that in the matched nontumor prostate tissues. In addition, tissues from bone metastasis of PCa had a high percentage of overexpressing COPS3. After knockdown of the COPS3 gene in 22rv1 and PC3 cells, two classic human PCa cell lines which had a high level of COPS3, the abilities of migration, invasion, and proliferation were inhibited. Finally, protein levels of phosphorylated P38 mitogen-activated protein kinase (MAPK) and N-cadherin were significantly decreased after knocking down the expression of COPS3, and the protein levels of E-cadherin were significantly increased. CONCLUSIONS: In conclusion, COPS3 may be closely related to the progress of PCa. Knockdown of COPS3 inhibited the progress of PCa through reducing the levels of phosphorylated P38 MAPK and impaired the epithelial-mesenchymal transition process.

Targeting silencing androgen receptor gene by shRNA with low-intensity focused ultrasonic irradiation inhibits growth of prostate cancer xenografts in nude mice.

The androgen receptor (AR) plays a pivotal role in prostate cancer, making it a potential therapeutic target. Short-hairpin RNA (shRNA) inhibits gene expression and offers a novel strategy to eradicate disease. Ultrasound-mediated gene transfection is a promising gene delivery method. This study sought to determine whether targeting silencing androgen receptor gene by shRNA with low-intensity focused ultrasonic irradiation could be used as effective therapy for prostate cancers in vivo. A plasmid-based short-hairpin RNA combined with low-intensity focused ultrasonic irradiation approach was used to specifically knock down the expression of AR in prostate cancer 22RV1 cells in vivo. The growth of 22RV1 tumors that had been subcutaneously xenografted was evaluated and expression level of AR was determined by immunohistochemical staining. The proliferative index (PI) and the apoptotic index (AI) were respectively derived from the percentage of positive cells by Ki-67 immunohistochemical staining and TUNEL assay. The plasmid-based AR shRNA administrated intravenously significantly inhibited the tumor growth and AR expression. These inhibitory effects of AR shRNA were augmented when the region of tumor received low-intensity focused ultrasound irradiation. Immunohistochemical staining and TUNEL assay confirmed AR shRNA with low-intensity focused ultrasonic irradiation exhibited growth-inhibitory, antiproliferative, and apoptotic effects on prostate cancer xenografts. The authors showed for the first time that the knockdown of AR expression by plasmid-based AR shRNA with low-intensity focused ultrasonic irradiation significantly suppressed the tumor growth of prostate cancer in vivo.

Overexpression of COPS3 promotes clear cell renal cell carcinoma progression via regulation of Phospho-AKT(Thr308), Cyclin D1 and Caspase-3.

The third subunit of the COP9 signalosome (COPS3) is associated with cell proliferation and tumorigenesis process in cancer. The present study showed that the expression level of COPS3 was upregulated in malignant cell lines and COPS3 overexpression was related with clinical stage, T stage, historical grade. Kaplan-Meier survival curves showed that COPS3 may function as a prognostic factor for overall survival. CCK-8 and colony formation assays revealed that knockdown of COPS3 in ACHN and 786-O significantly impacted proliferation in vitro. In addition, flow cytometry showed that inhibition of COPS3 induced G0/G1 arrest and promoted apoptosis. COPS3 may promote kidney cancer progression by altering Phospho-AKT(Thr308), Cyclin D1 and Caspase-3 expression. Collectively, Our findings suggest that COPS3 may be a new potential target of ccRCC.