Single-cell disulfidptosis regulator patterns guide intercellular communication of tumor microenvironment that contribute to kidney renal clear cell carcinoma progression and immunotherapy.

Background: Disulfidptosis, an emerging type of programmed cell death, plays a pivotal role in various cancer types, notably impacting the progression of kidney renal clear cell carcinoma (KIRC) through the tumor microenvironment (TME). However, the specific involvement of disulfidptosis within the TME remains elusive. Methods: Analyzing 41,784 single cells obtained from seven samples of KIRC through single-cell RNA sequencing (scRNA-seq), this study employed nonnegative matrix factorization (NMF) to assess 24 disulfidptosis regulators. Pseudotime analysis, intercellular communication mapping, determination of transcription factor activities (TFs), and metabolic profiling of the TME subgroup in KIRC were conducted using Monocle, CellChat, SCENIC, and scMetabolism. Additionally, public cohorts were utilized to predict prognosis and immune responses within the TME subgroup of KIRC. Results: Through NMF clustering and differential expression marker genes, fibroblasts, macrophages, monocytes, T cells, and B cells were categorized into four to six distinct subgroups. Furthermore, this investigation revealed the correlation between disulfidptosis regulatory factors and the biological traits, as well as the pseudotime trajectories of TME subgroups. Notably, disulfidptosis-mediated TME subgroups (DSTN+CD4T-C1 and FLNA+CD4T-C2) demonstrated significant prognostic value and immune responses in patients with KIRC. Multiple immunohistochemistry (mIHC) assays identified marker expression within both cell clusters. Moreover, CellChat analysis unveiled diverse and extensive interactions between disulfidptosis-mediated TME subgroups and tumor epithelial cells, highlighting the TNFSF12-TNFRSF12A ligand-receptor pair as mediators between DSTN+CD4T-C1, FLNA+CD4T-C2, and epithelial cells. Conclusion: Our study sheds light on the role of disulfidptosis-mediated intercellular communication in regulating the biological characteristics of the TME. These findings offer valuable insights for patients with KIRC, potentially guiding personalized immunotherapy approaches.

Exosomes-derived miR-548am-5p promotes colorectal cancer progression.

Exosomes are vital modulators in intercellular communication and microRNAs (miRNAs) are enriched within exosomes. MiRNAs are important participants in affecting colorectal cancer (CRC) progression, but the influence and latent mechanism of cancer-secreted exosomal miRNAs in colorectal cancer are not fully understood. miR-548am-5p has been reported to be differentially expressed in colon cancer and is indicated as a biomarker for colon cancer diagnosis at the early stage. In this study, we aimed to explore the role of exosomes-derived miR-548am-5p in CRC development. ISH and FISH were implemented to assess miR-548am-5p expression and location in CRC. CRC cells-secreted exosomes were identified via transmission electron microscopy and western blot. Colony formation, sphere formation and flow cytometry assessed the changes in proliferation, stemness and apoptosis of CRC cells. Bioinformatic analyses and mechanical experiments verified the binding of miR-548am-5p and RAR-related orphan receptor A (RORA). Our study identified miR-548am-5p was highly expressed in CRC tissues and cells. Tumor-derived exosomes expedited CRC cell proliferation and stemness along with secreted miR-548am-5p. Moreover, miR-548am-5p inhibition suppressed CRC cell proliferation and stemness while promoting cell apoptosis. RORA was the target mRNA of miR-548am-5p. Down-regulation of RORA was discovered in CRC and its expression was repressed by CRC cell-derived exosomes. As a result, our work elucidated that tumor-derived exosomal miR-548am-5p promoted CRC cell proliferation and stemness via targeting RORA, providing a valuable sight for CRC therapy.

Unveiling the role of GAS41 in cancer progression.

GAS41, a member of the human YEATS domain family, plays a pivotal role in human cancer development. It serves as a highly promising epigenetic reader, facilitating precise regulation of cell growth and development by recognizing essential histone modifications, including histone acetylation, benzoylation, succinylation, and crotonylation. Functional readouts of these histone modifications often coincide with cancer progression. In addition, GAS41 functions as a novel oncogene, participating in numerous signaling pathways. Here, we summarize the epigenetic functions of GAS41 and its role in the carcinoma progression. Moving forward, elucidating the downstream target oncogenes regulated by GAS41 and the developing small molecule inhibitors based on the distinctive YEATS recognition properties will be pivotal in advancing this research field.

Head-to-head immunogenicity comparison of an Escherichia coli-produced 9-valent human papillomavirus vaccine and Gardasil 9 in women aged 18-26 years in China: a randomised blinded clinical trial.

BACKGROUND: An Escherichia coli-produced human papillomavirus (HPV) 16 and 18 bivalent vaccine (Cecolin) was prequalified by WHO in 2021. This study aimed to compare the immunogenicity of the E coli-produced HPV 9-valent vaccine Cecolin 9 (against HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58) with Gardasil 9. METHODS: This was a randomised, single-blind trial conducted in China. Healthy non-pregnant women aged 18-26 years, who were not breastfeeding and with no HPV vaccination history, were enrolled in the Ganyu Centre for Disease Control and Prevention (Lianyungang City, Jiangsu Province, China). Women were stratified by age (18-22 years and 23-26 years) and randomly assigned (1:1) using a permutated block size of eight to receive three doses of Cecolin 9 or Gardasil 9 at day 0, day 45, and month 6. All participants, as well as study personnel without access to the vaccines, were masked. Neutralising antibodies were measured by a triple-colour pseudovirion-based neutralisation assay. The primary outcomes, seroconversion rates and geometric mean concentrations (GMCs) at month 7, were analysed in the per-protocol set for immunogenicity (PPS-I). Non-inferiority was identified for the lower limit of the 95% CI of the GMC ratio (Cecolin 9 vs Gardasil 9) at a margin of 0·5 and a seroconversion rate difference (Cecolin 9-Gardasil 9) at a margin of -5%. This study was registered at ClinicalTrials.gov (NCT04782895) and is completed. FINDINGS: From March 14 to 18, 2021, a total of 553 potential participants were screened, of which 244 received at least one dose of Cecolin 9 and 243 received at least one dose of Gardasil 9. The seroconversion rates for all HPV types in both groups were 100% in the PPS-I, with the values of the lower limits of 95% CIs for seroconversion rate differences ranging between -1·8% and -1·7%. The GMC ratios of five types were higher than 1·0, with the highest ratio, for HPV 58, at 1·65 (95% CI 1·38-1·97), and those of four types were lower than 1·0, with the lowest ratio, for HPV 11, at 0·79 (0·68-0·93). The incidence of adverse reactions in both groups was similar (43% [104/244] vs 47% [115/243]). INTERPRETATION: Cecolin 9 induced non-inferior HPV type-specific immune responses compared with Gardasil 9 and is a potential candidate to accelerate the elimination of cervical cancer by allowing for global accessibility to 9-valent HPV vaccinations, especially in low-income and middle-income countries. FUNDING: National Natural Science Foundation, Fujian Provincial Natural Science Foundation, Xiamen Science and Technology Plan Project, Fundamental Research Funds for the Central Universities, CAMS Innovation Fund for Medical Sciences of China, and Xiamen Innovax.

Spinal infection caused by Coxiella burnetii.

BACKGROUND: Spinal infection caused by Coxiella burnetii is rare and difficult to diagnose. Here we reported a case of spinal infection from Coxiella burnetii detected by the metagenomic next-generation sequencing (mNGS). CASE PRESENTATION: A 66-year-old male farmer with no medical history reported severe sharp low back pain, numbness and lower limb weakness for three years. Magnetic resonance imaging (MRI) revealed bone destruction and spinal cord compression within L1 and L2. mNGS testing showed that the inspected specimen collected from spinal lesion was detected positively for Coxiella burnetii. After receiving the combined treatment of antibiotic therapy and surgical intervention, the patient recovered well, and the sagittal MRI showed that vertebral edema signals disappeared and the graft of bone fused 16 months after surgery. CONCLUSION: The mNGS may be benefit for early diagnosis and intervention of non-specific spinal infection, and future studies should validate its effectiveness for clinical use in spinal infections. Additionally, antibiotic therapy combined with surgical intervention plays an important role on the treatment of spinal infection caused by Coxiella burnetii.

Expression of the Circadian Clock Gene ARNTL associated with DNA repair gene and prognosis of patient with osteosarcoma.

PURPOSE: The study objects were to explore the correlation between the biological role of clock genes and clinical indicators in patients with osteosarcoma (OS). METHODS: We acquired the clinical information and RNA sequencing data of OS samples from the TARGET database. The protein-protein interaction (PPI) network and expression correlation analysis of clock genes were performed. Then, the functional enrichment analysis of clock genes was analyzed. The survival analysis of clock genes in patients of OS was carried out by univariate cox regression, Kaplan-Meier (KM) curve and multivariate cox regression methods. Moreover, the spearmen correlation analysis was performed to explore the correlation between clock genes and DNA repair genes in patients with OS. RESULTS: The PPI network and expression correlation analysis of clock genes indicated that the clock genes were highly correlated with each other. The survival analysis of clock genes found that clock gene ARNTL is a protective factor for the prognosis of patients with OS. We found that ARNTL was positively related to DNA repair genes and was involved in the biological process of DNA damage repair in patients with OS. CONCLUSIONS: ARNTL may affect the prognosis and chemotherapy response of patients with OS by regulating DNA repair pathways.

[Retracted] MicroRNA­154 functions as a tumor suppressor in osteosarcoma by targeting Wnt5a.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the western blotting data featured in Fig. 5B and C, and also in Fig. 6B, were strikingly similar to data appearing in different form in other articles by different authors at different research institutes. Owing to the fact that the contentious data in the above article were already under consideration for publication, or had already been published, elsewhere prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Oncology Reports 35: 1851­1858, 2016; DOI: 10.3892/or.2015.4495].

Erratum to "Identifying biomolecules and constructing a prognostic risk prediction model for recurrence in osteosarcoma" [J. Bone Oncol. 26 (2021) 100331].

[This corrects the article DOI: 10.1016/j.jbo.2020.100331.].

Identifying biomolecules and constructing a prognostic risk prediction model for recurrence in osteosarcoma.

INTRODUCTION: Osteosarcoma is a high-morbidity bone cancer with an unsatisfactory prognosis. The aim of this study is to develop novel potential prognostic biomarkers and construct a prognostic risk prediction model for recurrence in osteosarcoma. METHODS: By analyzing microarray data, univariate and multivariate Cox regression analyses were performed to screen prognostic RNA signatures and to build a prognostic model. The RNA signatures were validated using Kaplan-Meier curves. Then, we developed and validated a nomogram combining age, recurrence, metastatic, and Prognostic score (PS) models to predict the individual's overall survival at the 3- and 5-year points. Pathway enrichment of RNA was conducted based on the significant co-expressed RNAs. RESULTS: A total of 319 mRNAs and 14 lncRNAs were identified in the microarray data. One lncRNA (LINC00957) and six mRNAs (METL1, CA9, B3GALT4, ALDH1A1, LAMB3, and ITGB4) were identified as RNA signatures and showed good performances in survival prediction for both the training and validation cohorts. Cox regression analysis showed that the seven RNA signatures could independently predict overall survival. Furthermore, age, recurrence, metastatic, and PS models were identified as independent prognostic factors via univariate and multivariate Cox analyses (P < 0.05) and included in the prognostic nomogram. The C-index values for the 3- and 5-year overall survival predictions of the nomogram were 0.809 and 0.740, respectively. CONCLUSIONS: The current study provides the novel potential of seven RNA candidates as prognostic biomarkers. Nomograms were constructed to provide accurate and individualized survival prediction for recurrence in osteosarcoma patients.

Occurrence of multidrug-resistant tuberculous meningitis associated with injury during spinal surgery: A case report.

Here we describe a case of multidrug-resistant tuberculous meningitis associated with injury inflicted during spinal surgery. A 54-year-old man was diagnosed with multidrug-resistant spinal tuberculosis (TB). Anterior debridement and fusion with posterior fusion and instrumentation were conducted to remove damaged bone and TB-associated granulomatous tissue. After surgical decompression, a lancet wound (about 5mm in length) was discovered in the cerebral dura mater at the L3 position of the vertebral body. At four weeks post-surgery, the patient experienced fever, hemiparesis, and aphasia. Cerebrospinal fluid (CSF) findings were consistent with TB meningitis, while in vitro susceptibility test results confirmed that the patient had multidrug-resistant TB. Our data highlight a possible TBM infection associated with a surgical lesion in a spinal TB patient. Rapid molecular diagnostics are urgently needed to formulate efficacious regimens for treating these patients.

A novel risk score model based on eight genes and a nomogram for predicting overall survival of patients with osteosarcoma.

BACKGROUND: This study aims to identify a predictive model to predict survival outcomes of osteosarcoma (OS) patients. METHODS: A RNA sequencing dataset (the training set) and a microarray dataset (the validation set) were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, respectively. Differentially expressed genes (DEGs) between metastatic and non-metastatic OS samples were identified in training set. Prognosis-related DEGs were screened and optimized by support vector machine (SVM) recursive feature elimination. A SVM classifier was built to classify metastatic and non-metastatic OS samples. Independent prognosic genes were extracted by multivariate regression analysis to build a risk score model followed by performance evaluation in two datasets by Kaplan-Meier (KM) analysis. Independent clinical prognostic indicators were identified followed by nomogram analysis. Finally, functional analyses of survival-related genes were conducted. RESULT: Totally, 345 DEGs and 45 prognosis-related genes were screened. A SVM classifier could distinguish metastatic and non-metastatic OS samples. An eight-gene signature was an independent prognostic marker and used for constructing a risk score model. The risk score model could separate OS samples into high and low risk groups in two datasets (training set: log-rank p < 0.01, C-index = 0.805; validation set: log-rank p < 0.01, C-index = 0.797). Tumor metastasis and RS model status were independent prognostic factors and nomogram model exhibited accurate survival prediction for OS. Additionally, functional analyses of survival-related genes indicated they were closely associated with immune responses and cytokine-cytokine receptor interaction pathway. CONCLUSION: An eight-gene predictive model and nomogram were developed to predict OS prognosis.

Sea cucumber Cucumaria frondosa fucoidan inhibits osteosarcoma adhesion and migration by regulating cytoskeleton remodeling.

Osteosarcoma (OS) has been demonstrated to be difficult to cure due to its potently malignant metastasis. Therefore, new therapeutic approaches blocking the metastatic potential of OS are urgently required to improve the outcomes for OS patients. In the present study, the anti­metastatic capacity of sea cucumber (Cucumaria frondosa) fucoidan (Cf­Fuc) was evaluated on osteosarcoma cells by cell adhesion assay, Transwell assay and U2OS cell migration assay. The underlying mechanism on the dynamic remodeling of the cytoskeleton was also explored. The present data indicated that Cf­Fuc could block the U2OS osteosarcoma cell adhesion to fibronectin and significantly inhibit U2OS cell migration. Cf­Fuc greatly impaired the migration capacity of U2OS cells, and the migrated distance and velocity of Cf­Fuc­treated cells were markedly reduced. Also, Cf­Fuc could impair the dynamic remodeling of the cytoskeleton possibly by suppressing the phosphorylation of focal adhesion kinase and paxillin, as well as the activation of the Rac1/PAK1/LIMK1/cofilin signaling axis. Collectively, the present findings provide a novel therapeutic potential of C. frondosa fucoidan for osteosarcoma metastasis.

PD­L1/PD­1 axis serves an important role in natural killer cell­induced cytotoxicity in osteosarcoma.

Osteosarcoma is a serious malignancy in pediatric patients, which comprises 2.4% of fatal cancer in children and achieves 20% of all primary bone cancers. In the present study, we employed three human osteosarcoma cell lines MG­63, HOS and U2OS for susceptibility to cytolytic activity of freshly isolated healthy donor NK cells. Cells were lysed by NK cells in a dose dependent manner. MG­63 cells exhibited less susceptibility to NK cells than HOS and U2OS cells at all cell ratios. The specific mechanism underlying the effects of NK cells on osteosarcoma cells was determined by antibody blockage experiments. The results revealed that granzyme B was the key factor in the NK cell­induced cytotoxicity of human osteosarcoma cells. To the best of our knowledge, the present study is the first to investigate the expression of PD­L1 in MG­63, HOS and U2OS cells. The relative expression of the PD­L1 gene and protein in MG­63 cell was greater than HOS and U2OS cells. The specific lysis of human osteosarcoma cells induced by NK cells was enhanced when PD­L1/PD­1 was blocked by the PD­L1 antibody. The present study proposed that the PD­L1/PD­1 axis serves an important role in NK cell­induced cytotoxicity in osteosarcoma via granzyme B secretion. Our findings may contribute to the development of precise treatments for osteosarcoma based on the expression profile of PD­L1 in patients with this disease.

Oncogenic miR-744 promotes prostate cancer growth through direct targeting of LKB1.

Prostate cancer (PCa) is one of the most common malignancies worldwide, and with a limited number of treatments for this type of cancer, its incidence is rapidly increasing. Patients presenting with PCa are likely to experience disease recurrence, which represents a considerable clinical challenge. MicroRNAs (miRNAs) have been widely characterized as a critical regulator in a number of types of cancer, including PCa. miRNA-744 (miR-744) has been reported to be involved in cancer regulation; however, its role in PCa remained poorly understood. In a recent study, it was demonstrated that miR-744 was overexpressed in prostate tissue from PCa patients when compared with the surrounding tissues, and knockdown of miR-744 resulted in reduced cell growth. In addition, an increased population of apoptotic cells was detected upon miR-744 knockdown, together with a decrease in cell proliferation. Cell cycle analysis demonstrated a higher number of cells in the G1 phase and lower numbers in the S phase following miR-744 silencing. The levels of key proteins involved in cell cycle progression (cyclin D1, cyclin-dependent kinase 4, and proliferating cell nuclear antigen) were increased, whereas those proteins responsible for cell cycle inhibition (cyclin-dependent kinase inhibitor p21) were decreased. The tumor suppressor liver kinase B1 (LKB1) was revealed to be a potential target of miR-744, suggesting its potential mechanism of action. LKB1 levels were negatively correlated with miR-744, and LKB1 was indicated to be a direct target of miR-744. Furthermore, it was revealed that by targeting LKB1, miR-744 may regulate adenosine monophosphate-activated protein kinase (AMPK); the AMPK signaling pathway was activated by miR-744 knockdown, with subsequent inhibition of the mammalian target of rapamycin (mTOR) signaling pathway. Taken together, these results demonstrated that miR-744 promoted cell growth through the AMPK signaling pathway, by targeting LKB1. The present study revealed a novel insight into the biological function of miR-744 in PCa, and that miR-744 may be a potential therapeutic target.

Sodium cantharidinate suppresses human osteosarcoma MG­63 cell proliferation and induces cell cycle arrest by inhibition of PI3K/AKT activation.

The function and mechanism of sodium cantharidininate (SC) underlying its suppression of human osteosarcoma (OS) MG­63 cells were investigated for the first time in the present study. MG­63 cell proliferation was determined by WST­1 assay post SC treatment at 0, 12, 24, 48 and 72 h. The results showed that SC effectively inhibited MG­63 cell proliferation and induced cell cycle arrest at the G0/G1 phase in a dose­dependent manner. Western blotting revealed that SC induced MG­63 cell cycle arrest at the G0/G1 phase by means of inhibition of cyclin D1, CDK4 and CDK6 expression. The expression of MAPK and AKT were evaluated using western blotting and FACS experiments to determine whether such signaling pathways are involved in the antiproliferative action of SC on MG­63 cells. SC significantly inhibited the phosphorylation of AKT, but not mTOR, JNK or P38. PI3K/AKT stimulator, IGF­1, reversed the SC­induced cell cycle arrest in the MG­63 cells. Collectively, our data indicate that the phosphorylation of AKT was inhibited by SC, consequently decreasing the expression of cyclin D1, CDK4 and CDK6 and inducing MG­63 cell G0/G1 phase arrest. SC has potential as a treatment agent for human osteosarcoma.

Ginsenoside Rb1 protects against spinal cord ischemia-reperfusion injury in rats by downregulating the Bax/Bcl-2 ratio and caspase-3 and p-Ask-1 levels.

The aim of this study was to confirm the effects of ginsenoside Rb1 on neural cell apoptosis in the spinal cord of rats with spinal cord ischemia-reperfusion injury (SCII) and to explore its potential mechanisms. A total of 100 healthy adult Sprague-Dawley (SD) rats were randomly divided into four groups: normal control (n = 10), sham-operated (n = 10), SCII model (n = 40), and ginsenoside Rb1-treated groups (n = 40). Basso, Beattie, Bresnahan (BBB) scale was used to examine rat hindlimb locomotor function. Nissl and Tunnel staining were used to observe neural cell injury and apoptosis, respectively, in the spinal cord of rats with SCII. Immunofluorescence staining was performed to detect the expression of Bax and Bcl-2. The levels of caspase-3 and phosphorylated Ask-1 (p-Ask-1) were detected by western blotting. Ginsenoside Rb1 prevented neural cell apoptosis in the spinal cord and improved hindlimb locomotor dysfunction of rats (P < .05). Moreover, SCII-induced upregulation of caspase-3 and p-Ask-1 levels and the Bax/Bcl-2 ratio were significantly decreased by ginsenoside Rb1 (P < .05). The protective effects of ginsenoside Rb1 on neural cells in the spinal cord of rats with SCII were mediated by the ginsenoside Rb1-induced downregulation of caspase-3 and p-Ask-1 levels and the Bax/Bcl-2 ratio.

MicroRNA-145-3p suppresses proliferation and promotes apotosis and autophagy of osteosarcoma cell by targeting HDAC4.

Studies have shown that miR-145-3p functions as a tumor suppressor and is associated with tumor growth and metastasis. This study intends to uncover the mechanism of a tumor suppressor of miR-145-3p. The expressions of miR-194 in osteosarcoma cell lines and tissues were monitored by real-time PCR. The proliferation ability was examined by MTT assay. The apoptosis and autophagy of cells were monitored by flow cytometry and microcopy, respectively. The regulation of miR-145-3p on HDAC4 was determined by luciferase assays and western blot assay. The results showed that miR-145-3p was significantly reduced in the osteosarcoma compared with the normal bone tissue. Overexpression of miR-145-3p significantly attenuated the proliferation and induced the apoptosis and autophagy of osteosarcoma cells. Furthermore, we demonstrated that miR-145-3p has inhibited the malignant behavior of osteosarcoma by down-regulating HDAC4 expression. These findings suggested that miR-145-3p may act as a tumor suppressor in osteosarcoma. MiR-145-3p/HDAC4 may be a novel therapeutic target in treatment of osteosarcoma.

Anterior fracture dislocation of the sacroiliac joint: A case report and literature review.

Publications describing the diagnosis and treatment of anterior dislocation of the sacroiliac joint are scarce. We report the case a 19-year-old female at 8 weeks' gestation who presented with anterior fracture dislocation of the right sacroiliac joint, posterior fracture dislocation of the left sacroiliac joint (crescent fracture), and incomplete abortion resulting from high energy trauma. Orthopedic surgery involved standard anterior sacroiliac joint plating using an ilioinguinal approach combined with a modified Stoppa approach. Three attempts at complete abortion failed. Complete abortion was eventually achieved by dilatation and curettage two weeks after orthopedic surgery. Our findings reveal a need to improve techniques for diagnosis and treatment of anterior fracture dislocation of the sacroiliac joint, so greater attention can be paid to the rapid and effective management of associated comorbidities, and those resulting from the initial trauma.

miR-214-5p Targets ROCK1 and Suppresses Proliferation and Invasion of Human Osteosarcoma Cells.

MicroRNAs (miRNAs) are small conserved RNAs regulating specific target genes in posttranscriptional levels. They have been involved in multiple processes of tumor progression, including cell proliferation. miR-214-5p (also miR-214*) is a newly identified miRNA, and its functions are largely unknown. In this study, we explore the role of miR-214-5p in the proliferation and invasion of human osteosarcoma (OS) cells. The results showed that miR-214-5p was sharply reduced in OS tissues and cell lines, compared with normal tissues and cell lines. In addition, the miR-214-5p mimic greatly increased the miR-214-5p level and significantly decreased the proliferation and invasion of HOS and G293 OS cells. In contrast, the miR-214-5p inhibitor had a completely opposite effect on the miR-214-5p level, cell proliferation, and cell invasion. Moreover, bioinformatics and luciferase reporter gene assays confirmed that miR-1908 targeted the mRNA 3'-UTR region of ROCK1, a characterized tumor promoter in OS. In conclusion, miR-214-5p was identified as a new tumor suppressor, which directly targeted ROCK1 and suppressed proliferation of human OS cells.

RASSF4 Overexpression Inhibits the Proliferation, Invasion, EMT, and Wnt Signaling Pathway in Osteosarcoma Cells.

RASSF4, a member of the RASSF family, is broadly expressed in normal tissues but often inactivated in human cancers. Despite various studies on RASSF4, its role in osteosarcoma remains unclear. Therefore, in this study, we investigated the effects of RASSF4 expression on osteosarcoma cells and explored the underlying mechanism. The results of our study showed that RASSF4 was lowly expressed in osteosarcoma tissues and cells. RASSF4 overexpression significantly inhibited proliferation, migration, and invasion as well as the EMT process in osteosarcoma cells. Meanwhile, we found that RASSF4 overexpression markedly decreased the protein expression of ß-catenin, cyclin D1, and c-Myc in osteosarcoma cells. In conclusion, our findings showed that RASSF4 overexpression inhibits proliferation, invasion, EMT, and Wnt signaling pathway in osteosarcoma cells. Thus, RASSF4 may be considered a novel target for osteosarcoma treatment.