IntroductionClear cell renal cell carcinoma (ccRCC) remains a clinically challenging malignancy due to late diagnosis and limited therapeutic options. This study aimed to investigate the role of DNER in the progression of ccRCC.MethodsBioinformatic analyses were integrated with experimental validation. Metabolism-related candidate genes were systematically screened to identify hub genes closely associated with metabolic pathway activity and immune cell infiltration. Both in vitro and in vivo functional assays were performed, along with mechanistic studies focusing on DNER-interacting proteins and downstream signaling pathways.ResultsBioinformatic analysis revealed that lipid metabolism and energy metabolism are key metabolic pathways significantly affecting the prognosis of ccRCC patients. Through systematic screening, DNER was identified as a hub gene strongly correlated with both metabolic pathway activity and immune cell infiltration. Functional experiments demonstrated that DNER promotes ccRCC cell proliferation both in vitro and in vivo. Mechanistically, DNER physically interacts with JAK2 and activates the JAK2/STAT3 signaling pathway, leading to STAT3 nuclear translocation and subsequent direct transcriptional upregulation of the glycolytic enzymes LDHA and PKM, thereby enhancing glycolytic flux. The increased lactate production drives macrophage polarization toward a pro-tumorigenic M2-like phenotype, establishing a signaling cascade that links tumor cell-intrinsic metabolic reprogramming to immunosuppressive microenvironment remodeling. Preliminary evidence also suggests that DNER overexpression may be associated with enhanced sensitivity of ccRCC cells to the PARP inhibitor Olaparib, although the underlying mechanism requires further investigation.DiscussionIn conclusion, DNER drives ccRCC progression by coupling glycolytic reprogramming with immunosuppressive microenvironment formation via the JAK2/STAT3 signaling axis, and may represent a potential therapeutic target for ccRCC.

POLE2 exhibits oncogenic properties. This study aimed to clarify its effects and underlying mechanisms in renal cell carcinoma (RCC). Using bioinformatics analyses, we predicted the relationship between POLE2 and autophagy, epithelial-mesenchymal transformation (EMT), and the AKT/mTOR pathway. The expression pattern of POLE2 was further verified in the clinical cohort comprising 94 tumor samples from patients with RCC. Following, we constructed in vivo and in vitro models to further investigate the potential mechanisms of POLE2 using a series of molecular biology approaches. The results showed that GINS1 was the downstream target of POLE2, and its overexpression reversed the inhibitory effects of POLE2 knockdown on RCC proliferation, metastasis, and EMT, while restoring the autophagy suppression. Furthermore, POLE2/GINS1 inhibited AKT/mTOR-mediated autophagy, thereby promoting EMT and lung metastasis of RCC. These findings provide a more comprehensive perspective on the genetic function of POLE2 in RCC progression.

Ovarian cancer is a gynecologic malignancy with high mortality and poor prognosis. Chemoresistance is a key cause of ovarian cancer recurrence and metastasis. It has been found that some bioactive peptides can inhibit the growth and metastasis of cancer cells and promote cell apoptosis, thus exerting anti-cancer effects. Tβ4–17 is a small polypeptide that we selected using ITRAQ technology, and its precursor protein is thymosin β4. This study mainly investigated its effect in combination with cisplatin (DDP) on the proliferation, migration and apoptosis of ovarian cancer resistant cells and related molecular mechanisms. Our results showed that Tβ4–17 peptide combined with DDP significantly inhibited the proliferation and migration of drug resistance cells in ovarian cancer, promoted apoptosis, and increased the chemo-sensitivity of ovarian cancer cells to DDP. In addition, qRT-PCR and Western blot showed that NF-κB was significantly highly expressed in DDP-resistant cells of ovarian cancer. After application of NF-κB inhibitors and activators, Western blot, CCK8, EDU fluorescence proliferation assay, and cell scratch assay showed that Tβ4–17 peptide down-regulated NF-κB p65 protein expression and inhibited cell proliferation and migration. In conclusion, our study demonstrates that Tβ4–17 peptide enhances the sensitivity of ovarian cancer cells to DDP by down-regulating NF-κB expression.

Chemo-resistance in ovarian cancer is currently a major obstacle to the treatment and recovery of ovarian cancer. Therefore, identifying factors associated with chemo-resistance in ovarian cancer may reverse chemo-sensitization. Using isobaric tags for relative and absolute quantitation (ITRAQ) technology, we found a small molecule peptide with annexin 1 (ANXA1) as a precursor protein. Then, we explored the effects and mechanisms of this small molecule peptide on the proliferation, apoptosis, and drug resistance of ovarian cancer resistant cells through CCK-8, EdU cell proliferation assay, Annexin V-FITC/PI assay, Western blot,qRT-PCR. ANXA114-26 was highly expressed in the serums of sensitive patients. ANXA114-26 promoted apoptosis of ovarian cancer cells and increased the sensitization of ovarian cancer cells to cisplatin. The ANXA114-26 and ANXA1 competitively bind formyl peptide receptors (FPR). ANXA114-26 decreased multidrug resistance-associated protein 1 (MRP1) expression in ovarian cancer cells through the FPR/Cyclin D1/NF-& kgreen;Bp65 pathway. We found a peptide derived named ANXA114-26 in the serum of ovarian cancer patients. It can reduce ovarian cancer cell proliferation and reduce MRP1 expression through the FPR/Cyclin D1/NF-& kgreen;Bp65 pathway.

Penile squamous cell carcinoma (PSCC) is a highly aggressive malignancy without effective treatment due to limited knowledge of its development and tumor microenvironment (TME). In this study, single-nucleus RNA sequencing (snRNA-seq) and high-resolution spatial transcriptomics are employed to comprehensively investigate the development trajectories and the TME. The results revealed that PSCC cells mimicked the differentiation and tissue organization of normal penile epithelium, independent of the human papillomavirus (HPV) infection status. Notably, a spatial subtype, Tum_1, appeared at early stage of tumor differentiation and in tumor-normal boundary regions. This subtype exhibited enhanced basal-like and stemness features and showed high LAMC2 expression, which activated laminin-integrin signaling via ITGA6/ITGB4, promoting tumor invasiveness. Furthermore, the results indicated that HPV-positive basal stem-like neoplasms dampened the immune function of T cells and macrophages, promoting an immunosuppressive environment that facilitates tumor progression. Supporting this, the patients with head and neck squamous cell carcinoma and lung squamous cell carcinoma who have high expression of HPV-positive Tum_1 signatures derived greater benefit from PD-1 blockade therapy. In summary, the findings provide a comprehensive spatial landscape of the PSCC TME and suggest potential treatment approaches targeting laminin-integrin interaction and immunotherapy, especially in HPV-positive patients.

This study aims to compare the safety and efficacy of robot-assisted partial nephrectomy (RAPN) and robot-assisted radical prostatectomy (RARP) using the Chinese surgical systems KangDuo-SR-2000 (KD-SR-2000) and EDGE MP1000 (MP1000) versus the Da Vinci Xi (DV-Xi) system, to explore viable alternative options to DV-Xi. This prospective, single-center, non-randomized clinical trial enrolled 261 patients who underwent RAPN or RARP from August 2023 to June 2024. All surgeries were performed by 3 surgeons. For RAPN, the primary outcome included surgical success, positive surgical margin (PSM), warm ischemia time (WIT) and conversion to open or laparoscopic surgery. The secondary outcome was estimated glomerular filtration rate (eGFR). For RARP, the primary outcome was surgical success without conversion to open or laparoscopic surgery, and the secondary outcomes included PSM and urinary continence recovery at 4 weeks post-catheter removal. Baseline demographics were comparable across the KD-SR-2000 group (n = 88), EDGE MP1000 group (n = 59) and DV-Xi group (n = 114). No significant differences observed in primary and secondary outcomes. However, operation time and suture time per stitch were longer in Chinese surgical systems for both RAPN and RARP compared to DV-Xi, and estimated blood loss (EBL) is higher in RAPN. Subgroup analyses indicated that performance differences were primarily attributed to the KD-SR-2000, with no significant differences observed between the MP1000 and DV-Xi. No severe complications (Clavien-Dindo grade ≥ 3) reported in any group. Chinese surgical systems provide a viable alternative, demonstrating non-inferiority compared to DV-Xi. ChiCTR2300074914; Registration Date: 2023-08-21.

Objective: To compare the perioperative outcomes between the MP1000 and da Vinci Xi surgical systems in robot-assisted partial nephrectomy (RAPN) and examine the MP1000 learning curve. Methods: In this prospective single-center study, 90 patients undergoing RAPN were equally allocated to the MP1000 (n = 45) or da Vinci Xi (n = 45) groups. Perioperative outcomes were analyzed, and the learning curve was assessed for MP1000 group operative times. Results: All procedures were completed without positive surgical margins. Significant discrepancies were observed in operation time, docking time, and estimated blood loss (p < 0.05). Postoperative estimated glomerular filtration rate (day 2), length of stay, and complication rate showed no significant differences. The cumulative sum curve was best fit by the equation y=-0.0002x4+0.0568x3-3.6013x2+69.011x, and R2=0.8806, with peak at case 13, and is subsequently delineated into a learning group (1-13 cases) and a skilled group (14-45 cases). The two groups exhibited comparable baseline characteristics. Conclusion: The MP1000 system is effective for partial nephrectomies, with all cases completed effectively. Meanwhile, surgeons with prior experience using the da Vinci Xi system achieve proficiency with the MP1000 after 13 procedures.

ObjectiveRadical cystectomy with ileal conduit is the current mainstay of treatment for muscle-invasive bladder cancer and is also a high-risk procedure. Existing studies have limited targeted assessment of the efficacy and safety of this procedure, and the patient population appropriate for this procedure is still poorly defined. We sought to longitudinally analyze differences in the efficacy and safety of radical cystectomy with ileal conduit by age subgroups to assess whether the age factor should be used as an exclusion criterion when selecting this procedure.Materials and methodsWe retrospectively examined the clinicopathological data of patients with MIBC treated with RC with IC at the Cancer Hospital of Harbin Medical University between February 2014 and October 2023. Additionally, we utilized clinical and pathological data from the SEER database (2000-2020) for external validation of our findings. Patients were categorized into elderly (≥70 years at diagnosis) and non-elderly (<70 years) groups. Statistical analyses included t-tests, non-parametric tests for continuous data, chi-square tests for categorical data, and Kaplan-Meier survival analysis.ResultsIn this study, 152 patients were included: 119 were categorized as non-elderly and 33 as elderly. For external validation, data from 416 patients in the SEER database were analyzed, with 172 classified as non-elderly and 244 as elderly. The results indicated that elderly patients were more likely to require ICU transfer postoperatively but exhibited a lower incidence of stoma inflammation. Additionally, both the data from our center and the external validation from the SEER database showed a concordance in cancer-specific survival (CSS) between the elderly and non-elderly groups. The efficacy of RC with IC was comparable in both elderly and non-elderly patients.ConclusionFor longitudinal age subgroups, RC with IC for both elderly and non-elderly MIBC had good efficacy and safety, and good quality of life after surgery. Although there are surgical and perioperative risks in elderly patients, there is no significant difference compared with non-elderly patients. In elderly patients requiring RC for bladder cancer, IC should remain the preferred mode of urinary diversion, and old age should not be used as an absolute exclusion criterion for IC.

Renal cell carcinoma (RCC) is the most common kidney cancer with high mortality rate. Pazopanib has been approved for the treatment of RCC. However, the underlying mechanism is not clear. Here, we report a novel finding by showing that treatment with Pazopanib could promote cellular senescence of the human RCC cell line ACHN. Cells were stimulated with 5, 10, and 20 mu M Pazopanib, respectively. Cellular senescence was measured using senescence-associated beta-galactosidase (SA-beta-Gal) staining. Western blot analysis and real-time polymerase chain reaction were used to measure the mRNA and protein expression of nuclear factor E2-related factor 2 (Nrf2), gamma H2AX, human telomerase reverse transcriptase (hTERT), telomeric repeat binding factor 2 (TERF2), p53 and plasminogen activator inhibitor (PAI). First, we found that exposure to Pazopanib reduced the cell viability of ACHN cells. Additionally, Pazopanib induced oxidative stress by increasing the production of reactive oxygen species, reducing the levels of glutathione peroxidase, and promoting nuclear translocation of Nrf2. Interestingly, Pazopanib exposure resulted in DNA damage by increasing the expression of gamma H2AX. Importantly, Pazopanib increased cellular senescence and reduced telomerase activity. Pazopanib also reduced the gene expression of hTERT but increased the gene expression of TERF2. Correspondingly, we found that Pazopanib increased the expression of p53 and PAI at both the mRNA and protein levels. To elucidate the underlying mechanism, the expression of Nrf2 was knocked down by transduction with Ad- Nrf2 shRNA. Results indicate that silencing of Nrf2 in ACHN cells abolished the effects of Pazopanib in stimulating cellular senescence and reducing telomerase activity. Consistently, knockdown of Nrf2 restored the expression of p53 and PAI in ACHN cells. Based on these results, we explored a novel mechanism whereby which Pazopanib displays a cytotoxicity effect in RCC cells through promoting cellular senescence mediated by Nrf2. image Pazopanib induced oxidative stress and nuclear translocation of Nrf2 in ACHN cellsPazopanib led to DNA damage and cellular senescence in ACHN cellsThe protective effects of Pazopanib are mediated by Nrf2

Prostate cancer, a leading cause of cancer-related mortality among men, is increasingly linked to epigenetic changes, particularly histone modifications that affect gene expression and tumor behavior. This review explores recent advances in understanding how aberrant histone acetylation, methylation, and other modifications contribute to prostate cancer progression, metastasis, and therapeutic resistance. By analyzing these modifications' roles in regulating critical pathways, this paper aims to elucidate their diagnostic and therapeutic potential, suggesting that targeted epigenetic therapies may offer new avenues for treatment.

Cancer invasion is driven by complex interactions between tumor cells and tumor microenvironment (TME), which promote cancer cell plasticity and remodel the TME to support invasive behavior. In bladder cancer, invasion into the muscularis propria reduces the five-year survival rate to below 30%. Despite this clinical significance, the molecular mechanisms underlying bladder cancer invasion remain poorly understood. Current studies predominantly focus on the comparison between non-invasive and invasive tumor tissue, leaving dynamic TME variation largely unexplored. Leveraging the capabilities of spatial information, we integrated Stereo-seq spatial transcriptomics with single-nucleus RNA sequencing (snRNA-seq) on whole-layers bladder cancer specimens. These integrated datasets delineated a spatially resolved whole-layers landscape of bladder cancer at single cell resolution, elucidating the localization and function of principle cell types during the invasive process. We discovered a bladder cancer invasive leading structure characterized by EPCAM and KRT17 co-expressing, whose plasticity is induced and maintained through interactions with POSTN+ cancer associated fibroblasts (CAFs) and APOE+ macrophages. Additionally, we uncovered the specific spatial distribution of different CAF subtypes during bladder cancer progression, highlighting their roles in shaping distinct TME. Notably, we revealed a progressive increase in immunosuppressive states from superficial to muscle-invading bladder tumors. Our findings underscore the orchestrated dynamics of bladder cancer progression driven by intricate tumor-stroma interactions within the TME. These insights provide a framework for understanding invasive behavior in other muscle-invasive cancers, guiding future research into shared mechanisms of tumor progression and microenvironmental remodeling.

Purpose The high recurrence rate after traditional transurethral resection of bladder tumor (TURBT) remains a challenge for management of non-muscle invasive bladder tumor (NMIBC). The aim of this study was to evaluate feasibility, efficacy and safety of surrounding en bloc resection using a general wire bipolar loop electrode and simultaneous intravesical chemotherapy. Methods We retrospectively analyzed data of 111 consecutive patients with NMIBC treated from June 2018 to December 2021. These patients underwent conventional TURBT and immediate intravesical chemotherapy (n = 45) or surrounding en bloc TURBT and simultaneous intravesical chemotherapy in the Urology Department of Harbin Medical University Cancer Hospital, The former and latter were defined as the conventional TURBT group and the surrounding en bloc TURBT group, respectively. All patients were followed up from 6 to 40 months, with an average of 24 months. Demographic characteristics, location and number of tumors, perioperative and postoperative data, pathological results and recurrence were documented. Results There were no significant differences in clinicopathological data between the conventional TURBT group (n = 45) and the surrounding en bloc TURBT group (n = 66). Operative time and complications associated with TURBT were comparable in the two groups. Recurrent tumors were found during follow-up in 2 (3.0%) of 66 patients in the surrounding en bloc group and 9 (20%) of 45 patients in the conventional group ( p < 0.05). Lower urinary tract symptoms developed in 2 (3.0%) of 66 patients after surrounding en bloc TURBT and in 11(24.4%) of 45 patients after conventional TURBT ( p < 0.05). Conclusion Surrounding en bloc TURBT and simultaneous intravesical chemotherapy might significantly decrease the recurrence rate of NMIBC, and showed favorable safety and tolerability profiles. The general bipolar loop electrode was appropriate to complete the procedure.

目的:探讨开放性零缺血结合同步切缝的肾部分切除术治疗复杂性孤立肾肾癌的可行性、安全性及优势.方法:回顾性分析2017年10月至2021年10月5例于哈尔滨医科大学附属肿瘤医院收治的解剖性和功能性孤立肾肾癌患者的临床资料,均采用开放性零缺血肾部分切除术和术中同步切缝技术,手术由同一术者完成,分析手术时间、术中失血量、术中及术后并发症、术后肿瘤学结果及肾功能指标的变化.结果:5例患者均成功采用开放性零缺血结合同步切缝的肾部分切除术,无中转肾动脉阻断和行挽救性肾切除术.手术时间为135～180 min,术中失血量为300～700 mL,平均失血量为450 mL.5例中1例肾门部肾癌患者术后第1天开始出现尿漏,当日膀胱镜下于输尿管内逆行留置F6双"J"管后,术后第2天尿漏消失.术后随访3～48个月,平均随访时间30.4个月,局部未见肿瘤复发,1例出现肋骨转移.与术前相比,术后各项肾功能指标无明显变化(P＞0.05).结论:开放性零缺血结合同步切缝的肾部分切除术在治疗复杂性孤立肾肾癌安全可行,特别适合复杂和肿瘤体积较大的肾癌,在保护肾脏功能和肿瘤治疗方面有着独特的优势.

TPS5093 Background: Penile squamous cell carcinoma (PSCC) is a highly aggressive disease that accounts for 95% of penile cancers and is characterized by a high risk of early locoregional spread and morbidity with subsequent potential for distant dissemination. The lymph node invasion is one of the most important factor that affects the prognosis of PSCC. Penile cancer patients with uninvolved inguinal lymph nodes had a 5-year survival rate of 66% compared with 27% for those with involvement, and penile cancer with the pelvic lymph node involvement have a worse 5-year survival rate that is typically less than 10%. Therefore, this study aims to reduce small lesions to reach the radical lymphadenectomy by camrelizumab combined with TIP in the neoadjuvant treatment of PSCC. Methods: In this single-arm, prospective, phase Ⅱ study, 34 patients with histological or cytological diagnosis of locally advanced PSCC (TX, N2-N3, M0), ECOG performance score of 0-1, planned to be recruited. Enrolled patients with inguinal and/or pelvic lymph node metastasis (positive percutaneous lymph node biopsy) after primary tumor resection of penile cancer were treated with combined therapy including camrelizumab (200 mg, iv, Q3W), paclitaxel (175 mg/m2, iv, Q3W), cisplatin (25 mg/m2, iv, Q3W) and ifosfamide (1200 mg/m2, iv, Q3W) for a total of 4 cycles. The primary endpoint is the rate of pathologic complete response (pCR). Secondary endpoints are event-free survival, overall survival, objective response rate, disease control rate and safety. On the basis of a threshold pCR rate of 13.6%, targeting an expected pCR of 34% and assuming 12 months follow-up, 80% power and a one-sided α = 0.05, this design requires 34 evaluable patients to be accrued over 3 years. Clinical trial information: ChiECRCT20210503.

Background: Renal cell carcinoma (RCC) is a prevalent malignancy with growing mortality and high metastasis. Ferroptosis has been identified as an essential process in cancer development, but the regulatory mechanism underlying the RCC progression remains obscure. The nanomaterial zinc oxide nanoparticles (ZONs) have presented anti-cancer function. Here, we identified the critical role of ZONs in promoting ferroptosis of RCC cells by regulating miR-27a-3p/YAP axis. Methods: The effect of ZONs on RCC was analyzed by qPCR, Western blot, MTT assays, colony formation assays, Flow cytometry analysis, transwell assays, wound healing assays, iron assays, lipid ROS detection, luciferase reporter gene assays, and tumor xenograft. Results: The treatment of ZONs repressed expression of GPX4 and SLC7A11 and enhanced ROS accumulation and iron/Fe2+ levels in RCC cells. Ferroptosis activator erastin repressed RCC cell viabilities and ZONs further repressed this effect. ZONs inhibited invasion and migration of RCC cells and treatment of ZONs represses RCC cell survival in vitro. ZONs suppressed RCC cell growth in tumorigenicity mouse model. Mechanically, ZONs down-regulated YAP expression by inducing miR-27a-3p, in which YAP overexpression and miR-27a-3p inhibition reverse ZONs - inhibited RCC cell survival in vitro. Discussion: Thus, we concluded that ZONs induced RCC cell ferroptosis to suppress RCC cell survival by targeting miR-27a-3p/YAP axis. The clinical significance of ZONs for the treatment of RCC is required to further study and may benefit the targeted therapy of RCC. (C) 2022 Published by Elsevier B.V. on behalf of King Saud University.

目的:探讨髂嵴上纵切口在后腹腔镜泌尿外科手术中的应用优势及推广.方法:选择2015年5月-2017年10月在我院采用三通道后腹腔镜途径治疗的肾上腺肿瘤及肾肿瘤患者159例,其中采用传统切口组72例,改良切口组87例,比较两组患者在取标本时间、切口长度(切口长度之和)、切口疼痛评分、切口并发症、下床活动时间、切口疝的发生率和切口复发率等方面的差异.结果:与传统切口组相比,在改良切口组采用肾上腺肿瘤切除术、肾部分切除术和肾癌根治术的病例具有更低的疼痛评分(P＜0.05),其中在接受肾上腺肿瘤切除术和肾部分切除术的患者显示有更短的取标本时间、切口长度和更早的下床活动时间(P＜0.05).改良切口组的患者无切口麻木及膨出,并且由于切口较低,位于腰带的后方及下方,仅能看到不明显的两工作套管的切口瘢痕.结论:后腹腔镜手术采用髂嵴上纵切口既可以用于进观察镜也可用于取标本,具有减轻疼痛、降低切口长度、加快术后活动时间和切口隐蔽的优点,值得广泛开展.

In recent years, the studies on ovarian cancer have made great progress, but the morbidity and mortality of patients with ovarian cancer are still very high. Due to the lack of effective early screening and detecting tools, 70% of ovarian cancer patients are diagnosed at an advanced stage. The overall survival rate of ovarian cancer patients treated with surgical combined with chemotherapy has not been significantly improved, and they usually relapse or resist chemotherapy. Therefore, a novel tumor marker is beneficial for the diagnosis and prognosis of patients with ovarian cancer. As the index of "liquid biopsy," circulating cell-free DNA/circulating tumor DNA (cfDNA/ctDNA) has attracted a lot of attention. It has more remarkable advantages than traditional methods and gives a wide range of clinical applications in kinds of solid tumors. This review attempts to illuminate the important value of cfDNA/ctDNA in ovarian cancer, including diagnosis, monitoring, and prognosis. Meanwhile, we will present future directions and challenges for detection of cfDNA/ctDNA.

Objectives: Human papillomavirus 16 (HPV 16) E2 is a transcriptional regulator that plays a key role in regulating a variety of biological responses. Hematopoietic cell-specific protein 1-related protein X-1 (HAX-1) is a mitochondrial membrane protein, and the HAX-1 gene is involved in the occurrence, growth, invasion, and metastasis of various human malignant tumors. The purpose of this study was to investigate the relationships among HPV 16 E2, the role of HAX-1 gene, and the underlying intracellular apoptotic mechanism of human cervical squamous carcinoma cells (C33a and SiHa). Methods: In this study, HAX-1 expression was examined using real-time polymerase chain reaction, Western blot, and immunohistochemical staining analysis. Apoptosis of cells was assessed by flow cytometry. The mitochondrial function was assessed by the mitochondrial copy number, reactive oxygen species (ROS) generation, the mitochondrial membrane potential (ΔΨm), and mitochondrial morphology. Results: Our study demonstrated that the expression of the HAX-1 gene was significantly increased in human cervical carcinoma tissues relative to noncancerous cervix tissues. HPV 16 E2 inhibited HAX-1 protein expression. Overexpression of HAX-1 increased the mitochondrial copy number, decreased the production of ROS, and maintained the integrity of the mitochondrial membrane and morphology. So, enhanced expression of the HAX-1 gene could abrogate the HPV 16 E2-induced cell apoptosis. Conclusion: Therefore, these data support a mechanism that HAX-1 plays a crucial role in HPV 16 E2-induced human cervical squamous carcinoma cell apoptosis in a mitochondrial-dependent manner.

Background: Pole2 gene is a subunit of DNA polymerases localized in the nucleus, which commonly present in DNA repair. The effect of pole2 in renal cell carcinoma (RCC) still remain unclear. Here we investigate its clinical significance, function in RCC cells and possible mechanism of effect. Methods: Using TCGA database, we identified that up-regulation of pole2 is associated with poor prognosis in ccRCC. We analyzed association between pole2 expression and T stage or Fuhrman grade. Thus, we investigate the effects of pole2 down-regulation on proliferation, cell cycles, apoptosis and possible mechanism in cells using lentivirus vector with shPole2. Results: Our study showed overexpression of pole2 in ccRCC samples, compared with normal kidney tissues, moreover, high expression of it related to high Fuhrman grade, also may predict poor prognosis in patients with ccRCC (p < 0.05). In cultured cells, knockdown of pole2 would result in inhibit of cell proliferation, increase the apoptosis of cells and arrest cell cycle at S phase. Importantly, knockdown pole2 can lead to down-regulation of p-mTOR and p-AKT expression. Conclusion: Taken together, our findings suggest that overexpression of pole2 may promote tumorgenesis and progress of ccRCC via AKT/mTOR signaling.

肾癌的发病率正在不断上升,透明细胞癌(CCRCC)是其最常见的病理类型,在此类癌的细胞质内可以观察到大量脂类聚集,肾癌细胞会改变其代谢脂质的能力,以支持肿瘤细胞增殖.在肾癌细胞中,许多脂质代谢的关键因子会发生改变,HIF能通过控制脂肪酸代谢来促进CCRCC脂质沉积,在RCC中SREBP1、FAS、ACLY过表达,FAS、ACC的抑制剂能够抑制肾肿瘤细胞的生长,SCD1抑制剂与mTOR抑制剂联合应用可能增强对肾肿瘤细胞的抑制作用,HADHA通过多种代谢途径导致胞质LDs下降,但仍然需要更多关于肾癌脂质代谢的研究,以获得新的治疗肾癌的分子靶点.