Efficacy and Safety of Neoadjuvant Subcutaneous Envafolimab in dMMR/MSI-H Locally Advanced Colon Cancer.

BACKGROUND: Neoadjuvant immunotherapy with programmed death-ligand 1 blockade for colon cancer, especially for mismatch repair-deficient (dMMR)/high microsatellite instability (MSI-H) colon cancer, has gained considerable attention recently. OBJECTIVE: This study aimed to assess the safety and efficacy of neoadjuvant subcutaneous envafolimab in patients with dMMR/MSI-H locally advanced colon cancer. METHODS: Patients with dMMR/MSI-H locally advanced colon cancer treated with envafolimab at Sun Yat-sen University Cancer Center and Yunnan Cancer Hospital from October 2021 to July 2023 were retrospectively reviewed and analyzed. The primary endpoint was the pathological complete response (CR) rate, and secondary endpoints were treatment-related adverse events and complete clinical response rate. RESULTS: Overall, 15 patients were analyzed. After neoadjuvant immunotherapy with envafolimab, six patients achieved a CR, with five partial responses, and four stable disease. Three patients achieving a complete clinical response chose to accept a "watch and wait" strategy, and surgery was performed in 12 patients. Postoperative pathology results revealed seven patients achieved pathological CRs, and five patients achieved tumor regression grade 2, with 66.7% of the total CR rate. The most common treatment-related adverse events were pruritus and rash (40%), with no severe cases. No recurrences occurred over a 7.9-month follow-up. CONCLUSIONS: Envafolimab yielded promising surgical outcomes and safety in dMMR/MSI-H locally advanced colon cancer, representing a promising treatment modality for this population.

Sodium Butyrate Inhibits the Malignant Proliferation of Colon Cancer Cells via the miR-183/DNAJB4 Axis.

Colorectal carcinoma (CRC) is one of the most common malignant tumors in the digestive tract. It was found that butyric acid could inhibit the expression of miR-183 to slow down malignant progression of CRC in the early stage. However, its regulatory mechanism remains unclear. This study screened the IC50 value of butyrate on inhibition of CRC cells malignant progression. Its inhibitory effects were detected by MTT assay, colony formation experiment, Transwell migration experiment, and apoptosis evaluation by flow cytometry. Next, the expressions of miR-183 and DNAJB4 were, respectively, determined in butyrate treated and miR-183 analog or si-DNAJB4-transfected CRC cells to further detect the role of upregulated miR-183 or silencing DNAJB4 in CRC cells malignant progression. Subsequently, the targeted regulatory relationship between miR-183 and si-DNAJB4 was confirmed by bioinformatic prediction tools and double luciferase report genes analysis method. The regulatory mechanism of butyrate on miR-183/DNAJB4 axis signal pathway was evaluated in molecular level, and verified in nude mouse xerograft tumor model and immunohistochemical analysis tests of Ki67 positive rates. The results displayed that butyrate with increased concentration can hinder the proliferation and improve apoptosis of CRC cells by decreasing the expression of miR-183. Thus, butyrate reduces miR-183 expression and increases DNAJB4 expression via the miR-183/DNAJB4 axis, ultimately inhibiting the malignant progression and increasing apoptosis of CRC. While over expression of miR-183 downregulate the expression of DNAJB4, which can reverse the inhibitory effect of butyrate.

Locally advanced rectal cancer with dMMR/MSI-H may be excused from surgery after neoadjuvant anti-PD-1 monotherapy: a multiple-center, cohort study.

Objective: Examine patients with locally advanced rectal cancer (LARC) with deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) who received neoadjuvant immunotherapy (nIT), and compare the outcomes of those who chose a watch-and-wait (WW) approach after achieving clinical complete response (cCR) or near-cCR with those who underwent surgery and were confirmed as pathological complete response (pCR). Methods: LARC patients with dMMR/MSI-H who received nIT were retrospectively examined. The endpoints were 2-year overall survival (OS), 2-year disease-free survival (DFS), local recurrence (LR), and distant metastasis (DM). The efficacy of programmed cell death protein-1 (PD-1) inhibitor, immune-related adverse events (irAEs), surgery-related adverse events (srAEs), and enterostomy were also recorded. Results: Twenty patients who received a PD-1 inhibitor as initial nIT were examined. Eighteen patients (90%) achieved complete response (CR) after a median of 7 nIT cycles, including 11 with pCR after surgery (pCR group), and 7 chose a WW strategy after evaluation as cCR or near-cCR (WW group). Both groups had median follow-up times of 25.0 months. Neither group had a case of LR or DM, and the 2-year DFS and OS in each group was 100%. The two groups had similar incidences of irAEs (P=0.627). In the pCR group, however, 2 patients (18.2%) had permanent colostomy, 3 (27.3%) had temporary ileostomy, and 2 (18.2%) had srAEs. Conclusion: Neoadjuvant PD-1 blockade had high efficacy and led to a high rate of CR in LARC patients with dMMR/MSI-H. A WW strategy appears to be a safe and reliable option for these patients who achieve cCR or near-cCR after nIT.

Establishment and verification of prognostic model and ceRNA network analysis for colorectal cancer liver metastasis.

OBJECTS: Colorectal cancer (CRC) is one of the most common cancers in the world. Approximately two-thirds of patients with CRC will develop colorectal cancer liver metastases (CRLM) at some point in time. In this study, we aimed to construct a prognostic model of CRLM and its competing endogenous RNA (ceRNA) network. METHODS: RNA-seq of CRC, CRLM and normal samples were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database. Limma was used to obtain differential expression genes (DEGs) between CRLM and CRC from sequencing data and GSE22834, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses were performed, respectively. Univariate Cox regression analysis and lasso Cox regression models were performed to screen prognostic gene features and construct prognostic models. Functional enrichment, estimation of stromal and immune cells in malignant tumor tissues using expression data (ESTIMATE) algorithm, single-sample gene set enrichment analysis, and ceRNA network construction were applied to explore potential mechanisms. RESULTS: An 8-gene prognostic model was constructed by screening 112 DEGs from TCGA and GSE22834. CRC patients in the TCGA and GSE29621 cohorts were stratified into either a high-risk group or a low-risk group. Patients with CRC in the high-risk group had a significantly poorer prognosis compared to in the low-risk group. The risk score was identified as an independent predictor of prognosis. Functional analysis revealed that the risk score was closly correlated with various immune cells and immune-related signaling pathways. And a prognostic gene-associated ceRNA network was constructed that obtained 3 prognosis gene, 14 microRNAs (miRNAs) and 7 long noncoding RNAs (lncRNAs). CONCLUSIONS: In conclusion, a prognostic model for CRLM identification was proposed, which could independently identify high-risk patients with low survival, suggesting a relationship between local immune status and prognosis of CRLM. Moreover, the key prognostic genes-related ceRNA network were established for the CRC investigation. Based on the differentially expressed genes between CRLM and CRC, the prognosis model of CRC patients was constructed.

Single-cell sequencing reveals the immune microenvironment landscape related to anti-PD-1 resistance in metastatic colorectal cancer with high microsatellite instability.

BACKGROUND: The objective response rate of microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) patients with first-line anti-programmed cell death protein-1 (PD-1) monotherapy is only 40-45%. Single-cell RNA sequencing (scRNA-seq) enables unbiased analysis of the full variety of cells comprising the tumor microenvironment. Thus, we used scRNA-seq to assess differences among microenvironment components between therapy-resistant and therapy-sensitive groups in MSI-H/mismatch repair-deficient (dMMR) mCRC. Resistance-related cell types and genes identified by this analysis were subsequently verified in clinical samples and mouse models to further reveal the molecular mechanism of anti-PD-1 resistance in MSI-H or dMMR mCRC. METHODS: The response of primary and metastatic lesions to first-line anti-PD-1 monotherapy was evaluated by radiology. Cells from primary lesions of patients with MSI-H/dMMR mCRC were analyzed using scRNA-seq. To identify the marker genes in each cluster, distinct cell clusters were identified and subjected to subcluster analysis. Then, a protein‒protein interaction network was constructed to identify key genes. Immunohistochemistry and immunofluorescence were applied to verify key genes and cell marker molecules in clinical samples. Immunohistochemistry, quantitative real-time PCR, and western blotting were performed to examine the expression of IL-1ß and MMP9. Moreover, quantitative analysis and sorting of myeloid-derived suppressor cells (MDSCs) and CD8+ T cells were performed using flow cytometry. RESULTS: Tumor responses in 23 patients with MSI-H/dMMR mCRC were evaluated by radiology. The objective response rate was 43.48%, and the disease control rate was 69.57%. ScRNA-seq analysis showed that, compared with the treatment-resistant group, the treatment-sensitive group accumulated more CD8+ T cells. Experiments with both clinical samples and mice indicated that infiltration of IL-1ß-driven MDSCs and inactivation of CD8+ T cells contribute to anti-PD-1 resistance in MSI-H/dMMR CRC. CONCLUSIONS: CD8+ T cells and IL-1ß were identified as the cell type and gene, respectively, with the highest correlation with anti-PD-1 resistance. Infiltration of IL-1ß-driven MDSCs was a significant factor in anti-PD-1 resistance in CRC. IL-1ß antagonists are expected to be developed as a new treatment for anti-PD-1 inhibitor resistance.

Beneficial effect of pristimerin against the development of osteoporosis in ovariectomy-induced osteoporosis rats by the RANKL/TRAF6/NF-κB pathway.

Introduction: Osteoporosis is a major cause of bone fracture in post-menopausal women. We evaluated the effects of pristimerin treatment on ovariectomy-induced osteoporosis, and its possible molecular mechanism. Material and methods: Rats were ovariectomised and biochemical markers of bone formation were determined from serum samples. The microarchitectures of bone tissues were analyzed via micro-CT scans and Western blotting assays. The cytotoxic effects of pristimerin, the differentiation of osteoclasts, and bone reabsorption were evaluated in vitro using RAW 264.7 cells. Results: Treatment with pristimerin attenuated changes in markers of bone formation and reabsorption such as creatine kinase (CK), alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP), collagen type I fragments (CTX), bone Gla-protein (BGP), and osteocalcin (OC) in the serum of ovariectomised rats. It also appeared to restore the microarchitecture of bone tissue. The expression levels of TNF receptor-associated factor 6 (TRAF-6), nuclear factor κ light chain enhancer of activated B cells (NF-κB p65), and receptor activator of nuclear factor-κB ligand (RANKL) protein were significantly lower, while those of Akt and PI3K were significantly higher, in the bone tissues of the pristimerin-treated group than in negative controls. Pristimerin had no cytotoxic effect on RAW 264.7 cells and reduced the differentiation of osteoclasts, bone reabsorption, and translocation of p65 in RANKL-stimulated RAW 264.7 cells in vitro. Conclusions: Pristimerin reduces the effects of osteoporosis by restoring the altered RANKL/TRAF-6/NF-κB pathway in ovariectomised rats.

Efficacy and Safety of Neoadjuvant Monoimmunotherapy With PD-1 Inhibitor for dMMR/MSI⁃H Locally Advanced Colorectal Cancer: A Single-Center Real-World Study.

Objective: To explore the efficacy and safety of single-agent programmed cell death protein-1 (PD-1) inhibitor in the neoadjuvant treatment of patients with mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) locally advanced colorectal cancer (LACRC) through single-center large⁃sample analysis based on real⁃world data in China. Methods: This study was a retrospective, single-center, case series study. 33 colorectal cancer (CRC) patients with clinical stage of T3~4N0~2M0 treated in Yunnan Cancer Hospital from June 2019 to June 2021 were analyzed retrospectively. Among them, 32 patients were dMMR or MSI-H or both dMMR and MSI-H, and one patient was both dMMR and microsatellite stability (MSS) (excluded in the final analysis). All 32 patients received neoadjuvant immunotherapy (nIT) with single-agent PD⁃1 inhibitor. Results: Among the 32 patients, 8 (25%) were locally advanced rectal cancer (LARC) and 24 (75%) were locally advanced colon cancer (LACC); 4 (12.55%) were stage II and 28 (87.5%) were stage III. The median number of cycles of 32 patients with dMMR/MSI-H LACRC receiving nIT with single-agent PD-1 blockade was 6 (4~10), and the median number of cycles to achieve partial response (PR) was 3 (2~4). Among them, three LARC patients achieved clinical complete response (cCR) and adopted the watch-and-wait (W&W) strategy. The objective response rate (ORR) of the other 29 patients with radical surgery was 100% (29/29), the pathological response rate was 100% (29/29), the rate of major pathological response (MPR) was 86.2% (25/29), and the rate of pathological complete response (pCR) was 75.9% (22/29). The incidence of immune-related adverse events (irAEs) in 32 patients during nIT was 37.5% (12/32), while the incidence of irAEs in 22 patients with operation during adjuvant immunotherapy was 27.3% (6/22), all of which were grade 1~2. No grade 3 or above irAEs were occured. The median time from the last nIT to surgery was 27 (16~42) days. There were no delayed radical resection due to irAEs in these patients. All 29 patients achieved R0 resection. The incidence of surgical-related adverse events (srAEs) in perioperative period was 10.3% (3/29). Conclusions: Neoadjuvant monoimmunotherapy with PD-1 inhibitor has favorable ORR and pCR rate, and relatively low incidences of irAEs and srAEs for patients with dMMR/MSI-H LACRC, suggesting that this nIT regimen of single-agent PD-1 inhibitor is significantly effective and sufficiently safe.

miR-16-5p Suppresses Progression and Invasion of Osteosarcoma via Targeting at Smad3.

BACKGROUND: MicroRNAs are known to regulate carcinogenesis of osteosarcoma. Although, miR-16-5p is known to exert inhibitory effects on several forms of cancers, its effects on the growth and invasion of osteosarcoma have not been studied. METHODS: We collected human osteosarcoma specimens and adjacent tissues to detect the expression of miR-16-5p by real-time polymerase chain reaction, immunoblotting, and immunohistochemistry. The proliferation, migration, and invasion of MG63 and HOS cells following miR-16-5p overexpression and inhibition were detected with cell counting kit-8, wound healing assay, and Transwell assay, respectively. An expression vector carrying a mutated 3'-untranslated region of mothers against decapentaplegic homolog 3 (Smad3) was constructed. RESULTS: The results showed that miR-16-5p expression was downregulated in osteosarcoma tissues and cells as compared with adjacent counterparts, while Smad3 was overexpressed in osteosarcoma cells. The overexpression of miR-16-5p resulted in the inhibition of the proliferation, migration, and invasion of osteosarcoma cells and enhanced the therapeutic effect of cisplatin. These effects were attenuated with miR-16-5p expression inhibition. In cells transfected with miR-16-5p mimic, Smad3 expression decreased, while this effect was absent in the cells carrying mutated Smad3. CONCLUSIONS: Therefore, miR-16-5p inhibits the growth and invasion of osteosarcoma by targeting Smad3.

Role of the HIF­1α/SDF­1/CXCR4 signaling axis in accelerated fracture healing after craniocerebral injury.

The hypoxic state of the brain tissue surrounding craniocerebral injury induces an increase in the secretion of HIF­1α during the healing process. HIF­1α can promote mesenchymal stem cell (MSC) migration to ischemic and hypoxic sites by regulating the expression levels of molecules such as stromal cell­derived factor­1 (SDF­1) in the microenvironment. Stem cells express the SDF­1 receptor C­X­C chemokine receptor type 4 (CXCR4) and serve a key role in tissue repair, as well as a number of physiological and pathological processes. The present study aimed to determine the role of HIF­1α/SDF­1/CXCR4 signaling in the process of accelerated fracture healing during craniocerebral injury. Cultured MSCs underwent HIF­1α knockdown to elucidate its effect on the proliferative ability of MSCs, and the effect of SDF­1 in MSCs was investigated. It was also determined whether HIF­1α could promote osteogenesis via SDF­1/CXCR4 signaling and recruit MSCs. The results indicated that HIF­1α knockdown suppressed MSC proliferation in vitro, and SDF­1 promoted cell migration via binding to CXCR4. Furthermore, HIF­1α knockdown inhibited MSC migration via SDF­1/CXCR4 signaling. Considering the wide distribution and diversity of roles of SDF­1 and CXCR4, the present results may form a basis for the development of novel strategies for the treatment of craniocerebral injury.

A Practical Study of Diagnostic Accuracy: Scoliosis Screenings of Middle School Students by a Trained Nurse With a Smartphone Versus a Spine Surgeon With a Scoliometer.

STUDY DESIGN: Cross-sectional. OBJECTIVE: This study aimed to assess the accuracy of smartphone-aided diagnosis of scoliosis by a trained nurse compared with scoliometer-based diagnosis by a spine surgeon. SUMMARY OF BACKGROUND DATA: Many assessments have been developed to estimate the reliability of smartphone-aided measurements in diagnosing scoliosis. However, clinical studies assessing the accuracy of smartphone-aided diagnosis with radiographs or scoliometers are scarce. METHODS: A total of 2702 grade 7 students (mean age 13.56 yrs, range 13-15) at 10 middle schools were first screened with a smartphone by a trained nurse from the orthopedics department. Approximately half a year later, most of the students underwent a chest x-ray examination as part of a compulsory medical examination. Students with suspicious findings in either the first screen or the chest x-ray were recommended to a scoliosis clinic for single-blind tests, such as a forward bending test (FBT) and an analysis of the angle of trunk rotation (ATR) with a scoliometer, performed by an experienced spine surgeon. Finally, the Cobb method was conducted with full-spine radiographs to serve as the gold standard. RESULTS: The agreement between the first screening by the nurse and the second test by the spine surgeon was low in cases with a Cobb angle <10° (κ = 0.128 [0.04-0.22], P = 0.035) and fair in cases with a Cobb angle >10° (κ = 0.349 [0.19-0.50], P < 0.001). The results of receiver operating characteristic (ROC) curve analysis also suggested that these two tests were similar in their ability to diagnose scoliosis. However, when the Cobb angle cutoff was adjusted to 15°, the latter had markedly better diagnostic ability than the former. Overall, the sensitivity of the smartphone screening was not acceptable for recognizing scoliosis. CONCLUSION: This study revealed that smartphone-aided screening for scoliosis is risky. LEVEL OF EVIDENCE: 3.

Deacylcynaropicrin Inhibits RANKL-Induced Osteoclastogenesis by Inhibiting NF-κB and MAPK and Promoting M2 Polarization of Macrophages.

Inflammation can promote the maturity of osteoclasts and bone resorption in many bone disease such as osteoporosis and arthritis. Here, we aimed to investigate the inhibitory effects of deacylcynaropicrin (DAC) on osteoclastogenesis and bone resorption induced by RANKL. Bone-marrow-derived macrophages were used for assessing the influence of DAC on polarization of macrophages and osteoclastogenesis in vitro. Inducible nitric oxide synthase (iNOS) and CD206, as well as osteoclastogenesis markers, nuclear factor of activated T-cells 1 (NFATc1), and c-Fos, were qualitatively analyzed by immunofluorescence, flow cytometry, reverse transcription polymerase chain reaction, and Western blotting. The results showed that DAC significantly inhibited osteoclastogenesis by suppressing the expression levels of c-Fos and NFATc1 through nuclear factor-κB, c-Jun N-terminal kinase (JNK), and Akt pathway. Moreover, immunohistochemistry and enzyme-linked immunosorbent assays showed that DAC reduced the release of tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6 in vivo. Finally, DAC also promoted macrophage polarization from M1 to M2 types. In conclusion, these results demonstrated that DAC suppressed RANKL-induced inflammation and osteoclastogenesis and therefore it can be used as a potential treatment for osteoporosis, arthritis, osteolysis, and aseptic loosening of artificial prostheses.

Hypoxia changes chemotaxis behaviour of mesenchymal stem cells via HIF-1α signalling.

Mesenchymal stem cells (MSCs) have drawn great attention because of their therapeutic potential. It has been suggested that intra-venous infused MSCs could migrate the site of injury to help repair the damaged tissue. However, the mechanism for MSC migration is still not clear so far. In this study, we reported that hypoxia increased chemotaxis migration of MSCs. At 4 and 6 hours after culturing in hypoxic (1% oxygen) conditions, the number of migrated MSCs was significantly increased. Meanwhile, hypoxia also increased the expression of HIF-1α and SDF-1. Using small interference RNA, we knocked down the expression of HIF-1α in MSCs to study the role of HIF-1α in hypoxia induced migration. Our data indicated that knocking down the expression of HIF-1α not only abolished the migration of MSCs, but also reduced the expression of SDF-1. Combining the results of migration assay and expression at RNA and protein level, we demonstrated a novel mechanism that controls the increase of MSCs migration. This mechanism involved HIF-1α mediated SDF-1 expression. These findings provide new insight into the role of HIF-1α in the hypoxia induced MSC migration and can be a benefit for the development of MSC-based therapeutics for wound healing.

LncRNA B4GALT1-AS1 recruits HuR to promote osteosarcoma cells stemness and migration via enhancing YAP transcriptional activity.

OBJECTIVES: This study aims to reveal the roles and related mechanisms of LncRNA B4GALT1-AS1 in osteosarcoma (OS) cells stemness and migration. MATERIALS AND METHODS: Real-time quantitative PCR (RT-qPCR) was used to detect the expression of several LncRNAs in OS tissues and normal adjacent tissues and in OS mammospheres and cells. Cell viability, transwell migration, tumour spheres formation and in vivo tumour formation assays were used to examine the effects of LncRNA B4GALT1-AS1 on OS progression. In addition, RNA immunoprecipitation (RIP) and Luciferase reporter assays were performed to determine the binding site of RNA-binding protein HuR on B4GALT1-AS1 and transcriptional factor YAP. Immunofluorescence analysis was used to examine YAP nuclear-cytoplasm translocation. RESULTS: LncRNA B4GALT1-AS1 expression was significantly increased in OS tissues and cells spheres. Knockdown of B4GALT1-AS1 inhibited OS cells proliferation, migration, stemness and chemotherapeutic sensitivity. Mechanistically, B4GALT1-AS1 recruited HuR to enhance YAP mRNA stability and thus its transcriptional activity. CONCLUSIONS: We indicate that lncRNA B4GALT1-AS1 promotes OS cells stemness and migration via recruiting HuR to enhance YAP activity.

RNA-binding protein PUM2 suppresses osteosarcoma progression via partly and competitively binding to STARD13 3'UTR with miRNAs.

OBJECTIVES: This work aims to reveal the roles and related mechanisms of RNA binding protein PUM2 in osteosarcoma progression. MATERIALS AND METHODS: Transcriptome analysis based on RNA sequencing data, real-time quantitative PCR (RT-qPCR), and western blot analysis were used to detect the expression of RBPs and miRNAs in OS and normal adjacent tissues, and the correlation between them in OS tissues. RT-qPCR, western blot, cell viability, transwell migration, tumour spheres formation and in vivo tumour formation assays were used to examine the effects of RBP PUM2 on OS progression. Additionally, RNA immunoprecipitation (RIP) assay combined with RNA sequencing was performed to determine the binding site of RBP PUM2 on STARD13 3'UTR. Luciferase reporter and RIP assays were used to confirm the binding of miRNAs or PUM2 on STARD13 3'UTR. RESULTS: PUM2 and STARD13 expression was significantly decreased in OS tissues, and positively correlated. Overexpression of PUM2 or STARD13 3'UTR inhibited OS cells proliferation, migration, and stemness. Mechanistically, PUM2 competitively bound to STARD13 3'UTR with miR-590-3p and miR-9. The inhibition of PUM2 on OS cells progression was attenuated by STARD13 knockdown or related miRNAs overexpression. CONCLUSION: PUM2 suppresses OS progression via partly and competitively binding to STARD13 3'UTR with miRNAs.

Knockdown of HuR represses osteosarcoma cells migration, invasion and stemness through inhibition of YAP activation and increases susceptibility to chemotherapeutic agents.

This study aims to explore the roles and related mechanisms of HuR in osteosarcoma (OS) cells migration, invasion, stemness and chemotherapeutical sensitivity. Here, we found that HuR exhibited higher level in OS tissues compared with the adjacent normal tissues. Knockdown of HuR with lentivirus infection suppressed OS cells migration and invasion, and thus the epithelial-mesenchymal transition (EMT) process. Additionally, HuR knockdown inhibited OS cells stemness. Mechanistically, YAP was identified as a direct target of HuR in OS cells, and HuR knockdown decreased its expression. Moreover, YAP transcriptional activity was attenuated by HuR knockdown, and RNA immunization co-precipitation (RIP) assay showed that HuR directly bound with YAP. Importantly, YAP overexpression rescued the inhibition of HuR knockdown on OS cells migration, invasion and stemness. Furthermore, HuR knockdown enhanced adriamycin sensitivity in OS cells, this effect was attenuated by YAP overexpression too. Importantly, HuR and YAP expression was positively correlated in OS tissues. Therefore, HuR acts as a tumor promoter by enhancing YAP expression in OS cells.