Enzalutamide-resistant related lncRNA NONHSAT210528 promotes the proliferation and invasion of prostate cancer.

Background: As a new-generation androgen-receptor antagonist, enzalutamide is a first-choice drug for advanced prostate cancer (PCa) patients. However, secondary resistance to enzalutamide poses a new challenge in the treatment of cancer. Long non-coding RNA (lncRNA) regulates cell function through many levels and mechanisms, and also plays an important role in the biological behaviors of tumors. Methods: LncRNA microarrays were used to detect enzalutamide-resistant related lncRNA in Enzalutamide-resistant C4-2 (C4-2 ENZ-R) cells and corresponding parent cells. Cell Counting Kit 8, flow cytometry, and transwell assays were used to test the effect of lncRNA NONHSAT210528 on the function of PCa cells. RNA pulls down and the luciferase report gene was used to detect the competitive endogenous RNA (ceRNA) mechanism. The culture supernatant of C4-2 and C4-2b cells was transferred to the lower chamber for transwell assay of human umbilical endothelial cells (HUVECs). Results: The lncRNA microarray analysis showed that there were significant differences in the expression of many lncRNAs between the C4-2 ENZ-R and C4-2 cells. The real-time polymerase chain reaction (PCR) detection showed that the expression of lncRNA NONHSAT210528 was significantly higher in the C4-2 ENZ-R cells than the C4-2 cells. The Transwell assays showed that lncRNA NONHSAT210528 overexpression increased the invasion of the C4-2 and C4-2b cells. The cell-wound scratch and the transwell assays showed that the culture supernatant of C4-2 and C4-2b cells with overexpressed lncRNA NONHSAT210528 promoted the migration and invasion of HUVECs. Furthermore, lncRNA NONHSAT210528 regulated the expression of YOD1 dependent on miR-21. Conclusions: Enzalutamide-resistant related lncRNA NONHSAT210528 appears to promote the proliferation and invasion of PCa cells by functioning as a ceRNA and regulating the miR-21-5p/YOD1 signal pathway.

Upregulation of erythropoietin and erythropoietin receptor in castration-resistant progression of prostate cancer.

Hypoxia-induced erythropoietin signaling plays an important role in tumor growth and invasion. In the present study, we investigated the contribution of erythropoietin signaling pathway to castration-resistant prostate cancer and the development of a neuroendocrine phenotype. Immunohistochemical staining showed that the erythropoietin and erythropoietin receptor scores in castration-resistant prostate cancer and androgen-dependent prostate cancer were 7.55 versus 4.5 and 7.45 versus 5.9,respectively (P < 0.001). Furthermore, a cell proliferation assay was conducted, and the differential expression of erythropoietin and erythropoietin receptor in LNCaP cells and hypoxia-induced LNCaP cells was evaluated using western blot and quantitative real-time PCR. The proliferation capacity of hypoxia-induced LNCaP cells was similar in cultures of both fetal bovine serum and charcoal-stripped fetal bovine serum, suggesting that LNCaP cells acquired hypoxia-induced androgen-independent growth. After 2 weeks of hypoxic culture, LNCaP cells showed a neuroendocrine cell change and increased expression of neuron-specific enolase, erythropoietin, and erythropoietin receptor; knockdown of erythropoietin receptor reversed the hypoxia-induced upregulation of neuron-specific enolase in the LNCaP cells. In conclusion, the concurrent upregulation of erythropoietin and erythropoietin receptor in castration-resistant prostate cancer suggests that the erythropoietin/erythropoietin receptor autocrine loop plays an important role in the progression of castration resistance and is responsible for the development of a neuroendocrine phenotype.

Cuprous oxide nanoparticles inhibit prostate cancer by attenuating the stemness of cancer cells via inhibition of the Wnt signaling pathway.

Disordered copper metabolism plays a critical role in the development of various cancers. As a nanomedicine containing copper, cuprous oxide nanoparticles (CONPs) exert ideal antitumor pharmacological effects in vitro and in vivo. Prostate cancer is a frequently diagnosed male malignancy prone to relapse, and castration resistance is the main reason for endocrine therapy failure. However, whether CONPs have the potential to treat castration-resistant prostate cancer is still unknown. Here, using the castration-resistant PC-3 human prostate cancer cell line as a model, we report that CONPs can selectively induce apoptosis and inhibit the proliferation of cancer cells in vitro and in vivo without affecting normal prostate epithelial cells. CONPs can also attenuate the stemness of cancer cells and inhibit the Wnt signaling pathway, both of which highlight the great potential of CONPs as a new clinical castration-resistant prostate cancer therapy.

Effect of hepatitis B immunoglobulin on interruption of HBV intrauterine infection.

AIM: To evaluate the efficacy of hepatitis B immunoglobulin (HBIG) in interrupting hepatitis B virus (HBV) intrauterine infection during late pregnancy. METHODS: We allocated 112 HBsAg positive pregnant women into 2 groups randomly. Fifty seven cases in the HBIG group received 200 IU (unit) HBIG intramuscularly every 4 wk from the 28 wk of gestation to the time of delivery, while 55 cases in the control group received no special treatment. HBsAg, HBeAg, HBcAb, HBeAb, HBsAb and HBV DNA levels were tested in the peripheral blood specimens from all of the mothers at 28 wk of gestation, just before delivery, and in blood from their newborns within 24 h before administration of immune prophylaxis. RESULTS: The intrauterine infection rate in HBIG group and control group were 10.5% and 27.3%, respectively, with significant difference (P<0.05). It showed ascendant trend as HBV DNA levels in the peripheral blood increased before delivery. CONCLUSION: HBIG is potent to cut down HBV intrauterine infection rate significantly when administered to pregnant women regularly during late pregnancy. The possibility of HBV intrauterine infection increases if maternal blood HBV DNA> or =10(8) copies/mL.

Interruption of HBV intrauterine transmission: a clinical study.

AIM: To investigate the effect of hepatitis B virus (HBV) specific immunoglobin (HBIG) and lamivudine on HBV intrauterine transmission in HBsAg positive pregnant women. METHODS: Each subject in the HBIG group (56 cases) was given 200 IU HBIG intramuscularly (im.) every 4 weeks from 28-week (wk) of gestation, while each subject in the lamivudine group (43 cases) received 100 mg lamivudine orally (po.) every day from 28-wk of gestation until the 30(th) day after labor. Subjects in the control group (52 cases) received no specific treatment. Blood specimens were tested for HBsAg, HBeAg, and HBV-DNA in all maternities at 28-wk of gestation, before delivery, and in their newborns 24 hours before the administration of immune prophylaxis. RESULTS: Reductions of HBV DNA in both treatments were significant (P<0.05). The rate of neonatal intrauterine HBV infection was significantly lower in HBIG group (16.1 %) and lamivudine group (16.3 %) compared with control group (32.7 %) (P<0.05), but there was no significant difference between HBIG group and lamivudine group (P>0.05). No side effects were found in all the pregnant women or their newborns. CONCLUSION: The risk of HBV intrauterine infection can be effectively reduced by administration of HBIG or Lamivudine in the 3(rd) trimester of HBsAg positive pregnant women.