Apatinib and gamabufotalin co-loaded lipid/Prussian blue nanoparticles for synergistic therapy to gastric cancer with metastasis.

Due to the non-targeted release and low solubility of anti-gastric cancer agent, apatinib (Apa), a first-line drug with long-term usage in a high dosage often induces multi-drug resistance and causes serious side effects. In order to avoid these drawbacks, lipid-film-coated Prussian blue nanoparticles (PB NPs) with hyaluronan (HA) modification was used for Apa loading to improve its solubility and targeting ability. Furthermore, anti-tumor compound of gamabufotalin (CS-6) was selected as a partner of Apa with reducing dosage for combinational gastric therapy. Thus, HA-Apa-Lip@PB-CS-6 NPs were constructed to synchronously transport the two drugs into tumor tissue. In vitro assay indicated that HA-Apa-Lip@PB-CS-6 NPs can synergistically inhibit proliferation and invasion/metastasis of BGC-823 cells via downregulating vascular endothelial growth factor receptor (VEGFR) and matrix metalloproteinase-9 (MMP-9). In vivo assay demonstrated strongest anti-tumor growth and liver metastasis of HA-Apa-Lip@PB-CS-6 NPs administration in BGC-823 cells-bearing mice compared with other groups due to the excellent penetration in tumor tissues and outstanding synergistic effects. In summary, we have successfully developed a new nanocomplexes for synchronous Apa/CS-6 delivery and synergistic gastric cancer (GC) therapy.

The signature of pyroptosis-related gene prognostic and immune microenvironment in adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) has a low incidence but a poor prognosis. And ACC has complex clinical manifestations and limited treatment. Pyroptosis has a dual character and has both positive and negative effects on cancer. However, the role of pyroptosis-related genes (PRGs) in ACC and the impact on ACC progression remains unelucidated. This study performed systematic bioinformatics analysis and basic experimental validation to enable the establishment of prognostic models and demonstrate levels of immune infiltration. Pearson's correlation analysis was used to assess the association of PRGs with tumor immune infiltration, tumor mutation burden (TMB), microsatellite instability (MSI), and immune checkpoints. There 4 PRGs were upregulated, and 25 PRGs were downregulated in ACC. At the same time, we analyzed and reviewed the genetic mutation variation landscape of PRGs. Functional enrichment analysis was also performed to clarify the function of PRGs. Pyroptosis, the inflammatory response, the Toll-like receptor signaling pathway, and the NOD-like receptor signaling pathway are the functions and pathways mainly involved and exerted effects by these 33 PRGs. The results of the prognosis analysis revealed high expression of CASP3, CASP9, GSDMB, GSDMD, NLRC4, PRKACA, and SCAF11 caused a poor survival rate for ACC patients. The above seven PRGs were screened by the optimal λ value of LASSO Cox analysis, and the five selected genes (CASP3, CASP9, GSDMB, GSDMD, NLRC4) were involved in constructing a prognostic PRGs model which enables the overall survival in ACC patients can be predicted with moderate to high accuracy. Prognostic PRGs, especially CASP9, which is the independent factor of ACC prognosis, may be closely correlated with immune-cell infiltration, tumor mutation burden, microsatellite instability, and immune checkpoints. Quantitative Real-Time PCR (qRT-PCR), Western blot and immunohistochemical were performed to validate the mRNA expression levels of CASP9 in adjacent normal tissues and ACC tissues. According to the result of immune checkpoints analysis, NLRC4 and GSDMB may be identified as potential therapeutic targets. In conclusion, we established a prognostic model of PRG characteristics in ACC and analyzed the relationship between PRGs and immune infiltration. Through our study, it may be helpful to find the mechanism of pyroptosis in ACC.

The Predictive Significance of Prognostic Nutritional Index and Serum Albumin/Globulin Ratio on the Overall Survival of Penile Cancer Patients Undergoing Penectomy.

Objective: To assess the value of using the prognostic nutritional index (PNI) and serum albumin/globulin ratio (AGR) in predicting the overall survival (OS) of patients with penile cancer (PC) undergoing penectomy. Materials and methods: A retrospective analysis of 123 patients who were admitted to our hospital due to PC from April 2010 to September 2021 and who underwent penectomy were included in the study. The optimal cut-off value of the PNI and AGR was determined by receiver operating characteristic curve analysis. Kaplan-Meier analysis and the Cox proportional hazard model were used to evaluate the correlation between the PNI, AGR, and OS in patients with PC. Results: A total of 16 of the 123 patients died during the follow-up period, and the median follow-up time was 58.0 months. The best cut-off values of the PNI and AGR were set to 49.03 (95% confidence interval 0.705-0.888, Youden index = 0.517, sensitivity = 57.9%, specificity = 93.7%, p < 0.001) and 1.28 (95% confidence interval 0.610-0.860, Youden index = 0.404, sensitivity = 84.1%, specificity = 56.2%, p = 0.003). The Kaplan-Meier analysis showed that the OS of the patients in the high PNI group and the high AGR group was significantly higher than that of the patients in the low PNI group and the low AGR group (p < 0.001). The univariable analysis showed that the aCCI, the clinical N stage, the pathological stage, and the PNI, AGR, SII, and PLR are all predictors of OS in patients with PC (p < 0.05). The multivariable analysis showed that the PNI (risk rate [HR] = 0.091; 95% CI: 0.010-0.853; p = 0.036) and the AGR (risk rate [HR] = 0.171; 95% CI: 0.043-0.680; p = 0.012) are independent prognostic factors for predicting OS in patients with PC undergoing penectomy. Conclusions: Both the PNI score and the serum AGR are independent prognostic factors for predicting OS in patients with PC undergoing penectomy.

MicroRNA-124 inhibits cell proliferation, invasion and migration by targeting CAV1 in bladder cancer.

[This retracts the article DOI: 10.3892/etm.2018.6537.].

Schisandrin B suppresses gastric cancer cell growth and enhances the efficacy of chemotherapy drug 5-FU in vitro and in vivo.

Gastric cancer (GC) is a serious affliction worldwide and remains to be the fourth most common cancer with poor prognosis, especially in advanced stage. Chemotherapy is one of the main therapeutic means. The purpose of this study was to investigate the antitumor effects of Schisandrin B (Sch B) on GC cells both in vitro and in vivo, as well as the synergistic effect with 5-fluorouracil (5-FU), and to preliminarily explore the relevant mechanism of action. Our results showed that Sch B inhibited the growth, migration and invasion of GC cells. Besides, Sch B could effectively inhibit the phosphorylation of STAT3 (signal transducer and activator of transcription 3), induce autophagy, and enhance the efficacy of chemotherapy drug 5-FU in vitro and in vivo. Taken together, the findings indicate that Sch B displays potent antitumor activities. The co-administration of Sch B and 5-FU might be a promising way for future therapy of GC.

[Up-regulated expression of miR-576 inhibits ALK4 expression, regulates JAK/STAT signaling pathway and promotes proliferation and migration of prostatic cancer cells].

OBJECTIVE: To explore the mechanism of the action of the miR-576/ALK4 axis on the progression of prostate cancer (PCa). METHODS: PCa cells were transfected with miR-576 mimics/inhibitor, the proliferation and migration distance of the cells were detected by MTT and scratch wound healing assay, respectively. The targeted regulation effect of miR-576 on ALK4 was verified by dual-luciferase reporter assay. The effects of miR-576 on the mRNA and protein expressions and phosphorylation levels of the ALK4 and JAK/STAT signaling pathway factors JAK2 and STAT3 were determined by qPCR and Western blot, respectively. The C4-2 cells were co-treated with sh-ALK4 and Ruxolitinib for measurement of the proliferation and migration of the PCa cells. RESULTS: Bioinformatics analysis and binding site prediction showed that miR-576 was up-regulated in the PCa cells, and dual-luciferase reporter assay revealed its targeted regulation effect on ALK4 and its impact on the phosphorylation levels of JAK2 and STAT3. Overexpressed miR-576 promoted while knocked-down miR-576 inhibited the proliferation and migration of the PCa cells. sh-ALK4 increased the proliferation and migration of the cells, while Ruxolitinib suppressed the promoting effect of sh-ALK4. CONCLUSION: The expression of miR-576 is up-regulated in PCa, inhibits the expression of ALK4, regulates the activity of the JAK and STAT signaling pathways, and promotes the proliferation and migration of PCa cells.

[Ductal adenocarcinoma of the prostate: Report of 45 cases and review of the literature].

OBJECTIVE: To explore the clinical features, treatment and prognosis of ductal adenocarcinoma of the prostate (DAP) and get a deeper insight into the malignancy. METHODS: We retrospectively studied the clinical data on 45 cases of confirmed DAP, 26 in the high-risk group and 19 in the medium-risk group, treated from January 2013 to September 2020. We compared the time and rate of biochemical recurrence and the rate of imaging progression between the two groups of patients, and evaluated the effect of palliative transurethral bipolar plasma resection of the prostate (pTU-PKRP) on the lower urinary tract symptoms (LUTS). RESULTS: Of the 45 cases of DAP, 4 (8.9%) were of the simple type, and 41 (91.1%) complicated by prostatic acinar carcinoma (PAA). And of the latter 41 cases, 9 (21.9%) were complicated by neuroendocrine differentiation and another 4 (9.8%) by intraductal carcinoma. The time to biochemical recurrence was longer in the medium-risk than in the high-risk group (P < 0.05). No statistically significant differences were observed in the rates of biochemical recurrence and imaging progression between the two groups (P > 0.05). The maximum urinary flow rate (Qmax), postvoid residual urine volume (PVR), IPSS and QOL of the patients were significantly improved at 6 months after pTU-PKRP compared with the baseline (P < 0.05). CONCLUSION: Radical prostatectomy can improve the prognosis of early DAP, while for advanced DAP with serious LUTS, pTU-PKRP can improve the quality of life of the patients.

Sexual, physical, and overall adverse effects in patients treated with 5α-reductase inhibitors: a systematic review and meta-analysis.

Postfinasteride syndrome (PFS) is a term coined to characterize a constellation of reported undesirable sexual, physical, and neuropsychiatric side effects. In the present study, we conducted the meta-analysis to demonstrate whether the use of 5α-reductase inhibitors (5ARIs) increases the risk of PFS-like adverse effects. A search of studies published until May 10, 2020, was performed using PubMed, EMBASE, and the Cochrane Library. We included randomized controlled trials with at least one comparison between male patients receiving 5ARIs versus placebo for the treatment of benign prostatic hyperplasia (BPH) or androgenetic alopecia (AGA), and identified 34 studies from 28 articles that met our eligibility criteria. In the random-effects model, the overall use of 5ARIs exhibited a 1.87-fold risk of PFS-like adverse effects during the trial (95% confidence interval [CI]: 1.64-2.14). Regarding specific types of adverse effects, the use of 5ARIs had a 1.89-fold risk of sexual adverse effects (95% CI: 1.74-2.05) and was associated with an increased risk of physical adverse effects (relative risk [RR]: 1.31, 95% CI: 0.80-2.15), albeit without statistical significance. This meta-analysis helped to better define the adverse effects caused by 5ARIs. We concluded that the overall use of 5ARIs significantly increased the risk of PFS-like adverse effects in men with AGA or BPH during treatment. Enhanced awareness of and education on the PFS-like adverse effects are necessary for clinicians.

The prognostic nutritional index predicts the biochemical recurrence of patients treated with robot-assisted laparoscopic radical prostatectomy.

OBJECTIVE: To evaluate the prognostic nutritional index (PNI) in predicting the biochemical recurrence (BCR) of patients treated with robot-assisted laparoscopic radical prostatectomy (RALP). METHODS: The clinical data of 136 patients treated with RALP in the Department of Urology, The Third Xiangya Hospital of Central South University were retrospectively analyzed. The endpoint of observation was BCR. The area under the receiver operating characteristic (ROC) curve was evaluated to determine the optimal cutoff value of PNI. The correlation of the PNI with BCR was estimated using Kaplan-Meier analysis and Cox proportional hazards model. RESULTS: The optimal cutoff value of the PNI was 46.03 according to the ROC curve. (95% confidence interval: 0.604-0.805, Youden index = 0.401, sensitivity = 82.5%, specificity = 57.6%, p < 0.01). Multivariate Cox analysis showed that clinical staging, prostate-specific antigen, and PNI were independent prognostic factors for predicting BCR in patients treated with RALP. CONCLUSION: PNI is an independent prognostic factor for predicting BCR in patients treated with RALP. The incorporation of the PNI into risk assessments may provide additional prognostic information.

Fe-doped chrysotile nanotubes containing siRNAs to silence SPAG5 to treat bladder cancer.

BACKGROUND: For certain human cancers, sperm associated antigen 5 (SPAG5) exerts important functions for their development and progression. However, whether RNA interference (RNAi) targeting SPAG5 has antitumor effects has not been determined clinically. RESULTS: The results indicated that Fe-doped chrysotile nanotubes (FeSiNTs) with a relatively uniform outer diameter (15-25 nm) and inner diameter (7-8 nm), and a length of several hundred nanometers, which delivered an siRNA against the SPAG5 oncogene (siSPAG5) efficiently. The nanomaterials were designed to prolong the half-life of siSPAG5 in blood, increase tumor cell-specific uptake, and maximize the efficiency of SPAG5 silencing. In vitro, FeSiNTs carrying siSPAG5 inhibited the growth, migration, and invasion of bladder cancer cells. In vivo, the FeSiNTs inhibited growth and metastasis in three models of bladder tumors (a tail vein injection lung metastatic model, an in-situ bladder cancer model, and a subcutaneous model) with no obvious toxicities. Mechanistically, we showed that FeSiNTs/siSPAG5 repressed PI3K/AKT/mTOR signaling, which suppressed the growth and progression of tumor cells. CONCLUSIONS: The results highlight that FeSiNTs/siSPAG5 caused no activation of the innate immune response nor any systemic toxicity, indicating the possible therapeutic utility of FeSiNTs/siSPAG5 to deliver siSPAG5 to treat bladder cancer.

ZHX3 promotes the progression of urothelial carcinoma of the bladder via repressing of RGS2 and is a novel substrate of TRIM21.

Clinically, patients with urothelial carcinoma of the bladder (UCB) with tumor metastasis are incurable. To find new therapeutic strategies, the mechanisms underlying UCB invasion and metastasis should be further investigated. In this study, zinc finger and homeobox 3 (ZHX3) was first screened as a critical oncogenic factor associated with poor prognosis in a UCB dataset from The Cancer Genome Atlas (TCGA). These results were also confirmed in a large cohort of clinical UCB clinical samples. Next, we found that ZHX3 could promote the migration and invasion capacities of UCB cells both in vitro and in vivo. Mechanistically, coimmunoprecipitation (coIP) and mass spectrometry (MS) analysis indicated that ZHX3 was a target of tripartite motif 21 (TRIM21), which mediates its ubiquitination, and subsequent degradation. Notably, RNA-seq analysis showed that ZHX3 repressed the expression of regulator of G protein signaling 2 (RGS2). Generally, our results suggest that ZHX3 plays an oncogenic role in UCB pathogenesis and might serve as a novel therapeutic target for UCB.

Animal models of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms are common clinical concerns that affect aging men all over the world. The underlying molecular and cellular mechanisms remain elusive. Over the past few years, a number of animal models of BPH, including spontaneous model, BPH-induction model, xenograft model, metabolic syndrome model, mechanical obstruction model, and transgenic model, have been established that may provide useful tools to fill these critical knowledge gaps. In this review, we therefore outlined the present status quo for animal models of BPH, comparing the pros and cons with respect to their ability to mimic the etiological, histological, and clinical hallmarks of BPH and discussed their applicability for future research.

Immediate Transurethral Plasma Kinetic Enucleation of the Prostate Gland for Treatment of Benign Prostatic Hyperplasia-Associated Massive Hemorrhage: A Single-Center Experience.

Purpose: Benign prostatic hyperplasia-associated massive hemorrhage is a urological emergency. We evaluated the outcome from immediate transurethral plasma kinetic enucleation of the prostate gland (i-TUPKEP) for BHM treatment. Methods: We retrospectively analyzed the records of 49 patients with acute BMH who underwent i-TUPKEP between January 2014 and November 2018 at our institution. The hemostatic effect, International Prostate Symptom Score (IPSS), and quality of life (QoL) score were evaluated preoperatively as well as 3, 6, and 12 months postoperatively. Postoperative follow-up also included measurement of the peak flow rate (Qmax) and post-void residual urine volume (PVR). Clinical characteristics, weight of resected tissue, duration of bladder irrigation, duration of hospital stay, complications, as well as the time required for enucleation and resection, were recorded. Results: BMH causes were attributed to transurethral surgery (17/49, 34.7%), violent catheterization (13/49, 26.5%), cystoscopy (10/49, 20.4%), and urethral dilatation (9/49, 18.4%). Bleeding was from different sites of prostate-gland tissues during i-TURKEP. i-TUPKEP-controlled BMH effectively induced immediate, notable, and lasting improvements in the IPSS and QoL score. Qmax was close to normal, and the PVR was within the physiological range, postoperatively. Long-term complications were not observed. Conclusion: Our preliminary data suggest that i-TUPKEP is a feasible method for controlling BHM and relieving BPH symptoms.

[Neuroendocrine differentiated prostate adenocarcinoma: Report of 23 cases and review of the literature].

OBJECTIVE: To study the clinical features and prognosis of neuroendocrine differentiated prostate adenocarcinoma (NED/AdPC). METHODS: We retrospectively analyzed the clinical data on 23 cases of NED/AdPC treated between 2005 and 2018, among which, 18 had lower urinary tract symptoms (LUTS). RESULTS: All the 23 patients were diagnosed with NED/AdPC, including 2 cases of AdPC initially diagnosed and confirmed with neuroendocrine differentiation in a second pathological diagnosis after androgen deprivation therapy (ADT). In addition to hormonal therapy for all the cases, 3 of the patients were treated by radical prostatectomy combined with adjuvant chemo- and radiotherapy, 13 by palliative transurethral bipolar plasmakinetic resection of the prostate (pTU-PKRP), of whom 2 underwent a second pTU-PKRP and chemotherapy for castration resistance, 2 with chronic renal insufficiency by percutaneous nephrostomy because of extensive pelvic metastasis, and the other 5 by ADT alone or in combination with radiotherapy. During the follow-up of 7 to 60 months, 2 of the patients died of cancer progression and 1 of pulmonary infection, while the others survived with effective control of the tumor. CONCLUSIONS: Long-term ADT may induce neuroendocrine differentiation in AdPC patients. For early-stage NED/AdPC, radical prostatectomy combined with adjuvant therapy is a main therapeutic option, while for advanced NED/AdPC, pTU-PKRP in combination with ADT may relieve LUTS and improve the patients' quality of life.

Primary abdominal cocoon with cryptorchidism: a case report.

BACKGROUND: We report a rare case of primary abdominal cocoon with bilateral cryptorchidism. CASE PRESENTATION: The patient had a history of laparoscopic surgery for bilateral cryptorchidism 6 years earlier. He was admitted to the hospital again due to intestinal obstruction. Surgery was performed on the patient after the failure of conservative treatment. The patient was diagnosed with primary abdominal cocoon. Instead of the greater omentum, many cocoon-like tissues surrounding the bowel were seen during operation. Abdominal surgery can increase the risk of intestinal adhesion, which is one of the main causes of intestinal obstruction, especially in patients with abdominal cocoon. We hypothesize that the surgery 6 years earlier to address transabdominal bilateral cryptorchidism accelerated the patient's intestinal obstruction. CONCLUSION: This case implies that it is important for urologists to evaluate whether their patients exhibit abdominal cocoon before cryptorchidism surgery, to choose better surgical methods and reduce the risks of poor prognosis.

Honokiol-Chlorambucil Co-Prodrugs Selectively Enhance the Killing Effect through STAT3 Binding on Lymphocytic Leukemia Cells In Vitro and In Vivo.

The broad-spectrum DNA alkylating therapeutic, chlorambucil (CBL), has limited safety and shows lower therapy effect because of a short half-life while used in the clinic. Therefore, it is very necessary to develop a more efficient and safer type of CBL derivate against tumors with selective targeting of cancer cells. In addition, the natural product of honokiol (HN), the novel potent chemo-preventive or therapeutic entity/carrier, can target the mitochondria of cancer cells through STAT3 to prevent cancer from spreading and metastasizing. In this study, we designed and synthesized the honokiol-chlorambucil (HN-CBL) co-prodrugs through carbonate ester linkage conjugating with the targeted delivery help of the HN skeleton in cancer cells. Biological evaluation indicated that HN-CBL can remarkably enhance the antiproliferation of human leukemic cell lines CCRF-CEM, Jurkat, U937, MV4-11, and K562. Furthermore, HN-CBL can also selectively inhibit the lymphocytic leukemia (LL) cell survival compared to those mononuclear cells derived from healthy donors (PBMCs), enhance mitochondrial activity in leukemia cells, and induce LL cell apoptosis. Molecular docking and western blot study showed that HN-CBL can also bind with the STAT3 protein at some hydrophobic residues and downregulate the phosphorylation level of STAT3-like HN. Significantly, HN-CBL could dramatically delay leukemia growth in vivo with no observable physiological toxicity. Thus, HN-CBL may provide a novel and effective targeting therapeutic against LL with fewer side effects.

Downregulation of LINC01021 by curcumin analog Da0324 inhibits gastric cancer progression through activation of P53.

Curcumin is a safe, cost-effective natural agent with multiple targets that displays therapeutic potential in cancer. Recently, we reported a novel curcumin analog, Da0324, which exhibited significantly improved stability and anti-cancer activity. However, the molecular mechanism underlying the anti-cancer activity of Da0324 remains largely unknown. Long non-coding RNAs have been shown to play important roles in cancer development and progression and may be potential targets for cancer therapy. Here, we showed that Da0324 treatment down-regulated the expression of LINC01021 in gastric cancer cells. Da0324 treatment or knockdown of LINC01021 by antisense oligos significantly inhibited gastric cancer cell growth, and also up-regulated P53 expression and down-regulated Bcl-2 expression in vitro and in vivo. Furthermore, Da0324 treatment or knockdown of LINC01021 in gastric cancer cells suppressed cell migration, invasion and epithelial-mesenchymal transition (EMT), as well as induced apoptosis and autophagy. In addition, overexpression of LINC01021 promoted growth and EMT, inhibited P53 expression and increased Bcl-2 expression in gastric cancer cells. Finally, overexpression of LINC01021 reversed the anti-cancer effect of Da0324. Our findings indicate a novel anti-cancer mechanism for Da0324, and that LINC01021 might be a potential therapeutic target for the treatment of gastric cancer.

SLC12A5 interacts and enhances SOX18 activity to promote bladder urothelial carcinoma progression via upregulating MMP7.

Solute carrier family 12 member 5 (SLC12A5) has an oncogenic role in bladder urothelial carcinoma. The present study aimed to characterize the molecular mechanisms of SLC12A5 in bladder urothelial carcinoma pathogenesis. Functional assays identified that in bladder urothelial carcinoma SLC12A5 interacts with and stabilizes SOX18, and then upregulates matrix metalloproteinase 7 (MMP7). In vivo and in vitro assays were performed to confirm the effect of SLC12A5's interaction with SOX18 on MMP7-mediated bladder urothelial carcinoma progression. SLC12A5 was upregulated in human bladder tumors, and correlated with the poor survival of patients with bladder urothelial carcinoma tumor invasion and metastasis, promoted by SLC12A5 overexpression. We demonstrated that SLC12A5 interacted with SOX18, and then upregulated MMP7, thus enhancing tumor progression. Importantly, SLC12A5 expression correlated positively with SOX18 and MMP7 expression in bladder urothelial carcinoma. Furthermore, SLC12A5 expression was suppressed by miR-133a-3p. Ectopic expression of SLC12A5 partly abolished miR-133a-3p-mediated suppression of cell migration. SLC12A5-SOX18 complex-mediated upregulation on MMP7 was important in bladder urothelial carcinoma progression. The miR-133a-3p/SLC12A5/SOX18/MMP7 signaling axis was critical for progression, and provided an effective therapeutic approach against bladder urothelial carcinoma.

HMGN5 promotes IL-6-induced epithelial-mesenchymal transition of bladder cancer by interacting with Hsp27.

Bladder cancer (BC) is one of the most common cancers worldwide, with a high rate of recurrence and poor outcomes. High-mobility group nucleosome-binding domain 5 (HMGN5) is overexpressed in many cancers and could cause carcinogenesis in BC. By protein-protein-interaction (PPI) analysis, we found that heat shock protein 27 (Hsp27), also a crucial functional factor in BC carcinogenesis, is significantly related to HMGN5. Hsp27 is required for IL-6-mediated EMT via STAT3/Twist signaling in prostate cancer. Here, we hypothesize that HMGN5 may interact with Hsp27 to affect IL-6-induced EMT and invasion in BC via STAT3 signaling. In the present study, we found that HMGN5 and Hsp27 are highly expressed in BC tissues and positively correlated with each other. HMGN5 interacts with Hsp27 in vitro, to modulate the cell invasion and EMT in BC. Moreover, HMGN5 could modulate IL-6-Hsp27-induced EMT and invasion in BC cells by regulating STAT3 phosphorylation and STAT3 targeting of the Twist promoter. HMGN5 interacts with Hsp27 to promote tumor growth in a human BC xenograft model in nude mice. In summary, HMGN5 interacts with Hsp27 to promote IL-6-induced EMT, therefore promoting invasion in BC and contributing to the progression of BC.