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BACKGROUND: Role of aquaporin-8 (AQP8) in cervical cancer has not been fully elucidated. OBJECTIVE: We aim to explore the impacts of AQP8 on viability, apoptosis and metastasis in cervical cancer cells. METHODS: AQP8 protein expression in cervical carcinoma specimens and cell lines was detected by IHC and western blot analysis. Lentivirus-mediated transfection was used to upregulate and knockdown AQP8 in cells. Cell viability and apoptosis were assessed by CCK-8 and flow cytometry assays, respectively. Transwell experiments were conducted to investigate cell invasive and migratory capabilities. EMT-related markers were detected by western blot analysis. RESULTS: A strong positive of AQP8 protein expression was observed in cervical cancer tissues. Western blot analysis confirmed overexpression and knockdown of AQP8 in SiHa cells. AQP8-overexpressed SiHa cells displayed an enhanced viability, reduced apoptotic rate, increased invasive and migratory abilities. Knockdown of AQP8 inhibited the viability, promoted the apoptosis, and suppressed invasion and migration. Furthermore, AQP8 overexpression significantly upregulated vimentin and N-cadherin, and downregulated E-cadherin, which were reversed by AQP8 knockdown. CONCLUSIONS: AQP8 increases viability, inhibits apoptosis, and facilitates metastasis in SiHa cells. This may be associated with EMT-related markers regulated by AQP8. AQP8 could serve as a potential marker for cervical cancer progression.

Background The aim of this study is to describe a modified technique in ileal orthotopic bladder substitution with a new ureteroileal anastomosis. Case presentation After a classic open radical cystectomy with bilateral pelvic lymphadenectomy was performed extraperitoneally, a 56-cm ileal segment was used to construct the spheroidal shape bladder substitution. The 8-cm long proximal and distal ends of the ileal segment were used as afferent limbs. Two-centimeter ileal segments of afferent limbs were detubularized and transversally tubularized. The elongated ileal tube was anastomosed with the ureter in an end-to-end fashion. The pathway of the ureteroileal anastomosis was placed between the abdominal cutaneous fat and the anterior rectus muscular sheath. Perioperative data and long-term functional outcomes were assessed. Between December 2011 and December 2015, seven male patients underwent this procedure with a median 46 (30–77) months follow-up in our hospital. There was no difference between preoperative and postoperative estimated glomerular filtration rates (Z = − 1.693, P = 0.09). One of 14 sides had ureteroileal anastomotic stenosis; two of 14 sides in one patient had ureteroileal anastomotic stenosis caused by invasion of pelvic recurrence 15 months postoperatively. Reflux was completely prevented by placing pressure on the corresponding point on the abdominal surface when voiding urine in all patients. Conclusions We describe a feasible technique modification in detail, which provides some advantages for effective anti-reflux by mechanical finger pressing and abdominal contraction, a low incidence of stricture, and ease for a secondary operation in the long-term follow-up period.

Objective: To investigate the effect of peroxiredoxin 1 (PRDX1) on the biological behavior of cervical cancer cells and the possible mechanism. Materials and methods: The expression of PRDX1 in human cervical cancer tissues and adjacent non-tumor tissues were detected by immunohistochemistry (IHC). Lentivirus containing PRDX1-cDNA or shRNA against PRDX1 was constructed to overexpress or knockdown PRDX1 in SiHa cervical cancer cells. Cell proliferation was tested by CCK-8 and BrdU incorporation assay and cell apoptosis was evaluated by AnnexinV-PE /7AAD assay. Scratch wound and transwell invasion assay were used to test migration and invasion activity after PRDX1 was overexpressed or suppressed. Furthermore, the effect of PRDX1 on cell proliferation and apoptosis was also studied using a xenograft model of nude mice. Results: The expression of PRDX1 protein was significantly up-regulated in the tumor tissues compared with the paired adjacent non-tumor tissues. Meanwhile, PRDX1 overexpression was associated with tumor stage, lymphatic metastasis and differentiation. Overexpression of PRDX1 significantly promoted proliferation and inhibited apoptosis by increasing the expression of Nanog, proliferating cell nuclear antigen (PCNA), B-cell lymphoma-2 (Bcl-2) and downregulating the expression of Bcl2-associated X protein (BAX) in SiHa cervical cancer cells. Moreover, PRDX1 overexpression increased invasion and migration of SiHa cervical cancer cells via up-regulating the expression of Snail and matrix metalloprotein 9 (MMP-9) and down-regulating the expression of E-cadherin. Knockdown of PRDX1 resulted in the opposite results. The role of PRDX1 in promoting SiHa cervical cancer cell proliferation and inhibiting apoptosis has also been confirmed in vivo in a mouse xenograft model. Conclusions: PRDX1 promoted cell proliferation, migration, and invasion and suppressed apoptosis of cervical cancer possibly via regulating the expression of related protein.

Background: Our previous study demonstrated that the peroxiredoxin 6 (PRDX6) protein was downregulated in squamous cervical cancer samples after neoadjuvant chemotherapy compared with the expression level before chemotherapy. However, the effect of PRDX6 on the biological behavior of cervical cancer is still uncertain. Thus, the purpose of this study was to explore the functional impacts of PRDX6 gene on the biological behavior of cervical squamous cancer cells. Methods: An immunofluorescence assay was applied to evaluate the expression difference of PRDX6 between cervical cancer tissue and normal cervical tissue samples. A lentivirus was used to upregulate and downregulate PRDX6 expression in SiHa cells. Furthermore, the role of PRDX6 on cell proliferation, apoptosis, migration and invasion was evaluated. Additionally, the effect of PRDX6 on the progression of the cervical cancer was investigated via a xenograft model in BALB/c nude mice that either overexpressed or underexpressed PRDX6. Results: The expression of PRDX6 was generally increased in cervical cancer tissues. Furthermore, the overexpression of PRDX6 stimulated the proliferation, migration and invasion of cervical squamous cancer cells, and suppressed cell apoptosis. The opposite results were also obtained after successful knockdown of PRDX6. In addition, the overexpression of PRDX6 significantly promoted the growth of cervical carcinoma in vivo. Conclusions: PRDX6 promoted the proliferation, migration and invasion, and inhibited apoptosis in cervical cancer cells, indicating that PRDX6 is an important promoter of cervical cancer tumorigenicity.

Background: We previously revealed that the expression of galectin-1 (LGALS1) was significantly reduced after neoadjuvant chemotherapy treatment in cervical cancer patients. The objective of this study is to investigate the effects of LGALS1 expression on biological behaviors of cervical cancer cells. Methods: Immunohistochemistry and immunocytochemistry were performed to detect the expression of LGALS1 in cervical cancer tissues and cells (SiHa and C33A). Western blot analysis was performed to evaluate the efficacy of lentivirus-mediated upregulation or downregulation of LGALS1 in cervical cancer cells. Cell viability and proliferation were detected by CCK-8 and BrdU assays, respectively. Annexin V-FITC/PI apoptosis detection kit was employed to measure the apoptosis of cervical cancer cells. Transwell invasion and migration assays were also conducted to explore the invasive and migratory capabilities of cervical cancer cells. The expression of apoptosis- (Bcl-2 and Bax), invasion- (MMP-2 and MMP-9), and migration-related (Fascin and Ezrin) proteins, were detected by Western blot analysis. Xenograft mouse model of cervical cancer was generated to explore whether LGALS1 overexpression could promote tumor growth in vivo. Results: LGALS1 was overexpressed in cervical cancer tissues and cell lines compared to that in normal cervical tissues and epithelium cells. Upregulation of LGALS1 significantly promoted the cell proliferation, inhibited cell apoptosis, and enhanced the migratory and invasive abilities of both SiHa and C33A cells, whereas downregulation of LGALS1 led to the opposite results. The level of Bcl-2, MMP-2, MMP-9, Fascin, and Erzin expression was significantly upregulated in cervical cancer cells with LGALS1 overexpression, while converse results were obtained in LGALS1 knockdown cancer cells. In vivo study also showed that LGALS1 overexpression facilitated tumor growth of cervical cancer cells. Conclusion: Overexpression of LGALS1 significantly promoted and enhanced the aggressive features of cervical cancer both in vitro and in vivo, which may be associated with high expression of Bcl-2, MMP-2, MMP-9, Fascin, and Erzin proteins.

Ovarian cancer is one of the most lethal gynecologic tumors in women and has a poor prognosis. The purpose of our study was to identify new prognostic markers in ovarian cancer. We examined the prognostic roles of mRNA expression of the chromobox (CBX) family in patients with ovarian cancer utilizing the Kaplan-Meier plotter database. The prognostic values and expression levels of CBX members associated with prognosis were further evaluated using KM plotter in diverse subgroups and immunohistochemistry (IHC) analysis in ovarian carcinoma. The results revealed that elevated CBX1-3 mRNA expression may predict poor overall survival (OS) and progression-free survival (PFS) outcomes in patients with ovarian cancer. Notably, in women with ovarian cancer, increased CBX1 mRNA expression was linked to a short OS in all stages and in the grade II and grade III subgroups. Additionally, CBX2 and CBX3 were strongly related to short OS in stage III+IV patients, and a link between high CBX3 mRNA expression and unfavorable OS in grade II patients was observed. High expression levels of CBX1 and CBX3 were significantly associated with chemotherapy resistance in ovarian cancer patients. IHC staining showed that the CBX1-3 proteins were upregulated in serous ovarian carcinoma tissues compared with normal ovarian tissues. Therefore, our results indicated that CBX1-3 could be attractive biomarkers for predicting poor prognosis of ovarian cancer.

F-box proteins (FBPs) are proteins containing an F-box domain and are one of three subunits in SKP1–Cullin1–F-box protein (SCF) E3 ligase complexes. Accumulated evidence has shown that FBP regulates tumorigenesis and the progression of human cancer via ubiquitination and degradation of downstream substrates, which can be oncoproteins or tumor suppressors. Emerging evidence has revealed that noncoding RNAs (ncRNAs) govern the expression of FBP in human cancers. Specifically, microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs) have been shown to govern FBP expression in malignancies. Therefore, in this review article, we discuss how miRNAs target FBPs and participate in tumorigenesis and tumor progression. Moreover, we briefly highlight the role of lncRNAs and circRNAs in the regulation of FBPs in cancer. Therefore, targeting ncRNAs could be a novel approach to regulate FBPs for anticancer therapy.

BackgroundMYCN is an oncogenic transcription factor of the MYC family and plays an important role in the formation of tissues and organs during development before birth. Due to the difficulty in drugging MYCN directly, revealing the molecules in MYCN regulatory networks will help to identify effective therapeutic targets.MethodsWe utilized network controllability theory, a recent developed powerful tool, to identify the potential drug target around MYCN based on Protein-Protein interaction network of MYCN. First, we constructed a Protein-Protein interaction network of MYCN based on public databases. Second, network control analysis was applied on network to identify driver genes and indispensable genes of the MYCN regulatory network. Finally, we developed a novel integrated approach to identify potential drug targets for regulating the function of the MYCN regulatory network.ResultsWe constructed an MYCN regulatory network that has 79 genes and 129 interactions. Based on network controllability theory, we analyzed driver genes which capable to fully control the network. We found 10 indispensable genes whose alternation will significantly change the regulatory pathways of the MYCN network. We evaluated the stability and correlation analysis of these genes and found EGFR may be the potential drug target which closely associated with MYCN.ConclusionTogether, our findings indicate that EGFR plays an important role in the regulatory network and pathways of MYCN and therefore may represent an attractive therapeutic target for cancer treatment.

The nuclear speckle-type pox virus and zinc finger (POZ) protein (SPOP), a representative substrate-recognition subunit of the cullin-RING E3 ligase, has been characterized to play a dual role in tumorigenesis and cancer progression. Numerous studies have determined that SPOP suppresses tumorigenesis in a variety of human malignancies such as prostate, lung, colon, gastric, and liver cancers. However, several studies revealed that SPOP exhibited oncogenic function in kidney cancer, suggesting that SPOP could exert its biological function in a cancer type-specific manner. The role of SPOP in thyroid, cervical, ovarian, bone and neurologic cancers has yet to be determined. In this review article, we describe the structure and regulation of SPOP in human cancer. Moreover, we highlight the critical role of SPOP in tumorigenesis based on three major categories: physiological evidence (animal models), pathological evidence (human cancer specimens) and biochemical evidence (downstream ubiquitin substrates). Furthermore, we note that SPOP could be a promising therapeutic target for cancer treatment.