[Retracted] MicroRNA­199a­3p inhibits ovarian cancer cell viability by targeting the oncogene YAP1.

Following the publication of the above article, the authors have submitted a request that it be retracted on account of the fact that, when requested to do so, the first author was unable to provide the original data for this article. The Editor of Molecular Medicine Reports has agreed with the request that this article be retracted. Note that all the authors agree with the decision to retract this article. The Editor and the authors regret any inconvenience that this retraction will cause to the readership of the Journal. [Molecular Medicine Reports 23: 237, 2021; DOI: 10.3892/mmr.2021.11876].

Retraction Note: MicroRNA-199a-5p suppresses the cell growth of colorectal cancer by targeting oncogene Caprin1.

[This retracts the article DOI: 10.1007/s13205-020-02433-9.].

Sirtuin 2 promotes cell stemness and MEK/ERK signaling pathway while reduces chemosensitivity in endometrial cancer.

PURPOSE: Sirtuin 2 (SIRT2) is functionally important in cancer progression and treatment resistance as an NAD+-dependent deacetylase, whereas its role in endometrial cancer (EC) is limitedly investigated. This study aimed to evaluate the regulatory role of SIRT2 on cell stemness and chemosensitivity in EC. METHODS: SIRT2 expression was detected in human EC cell lines, including Ishikawa, AN3CA, HEC1A, KLE, and normal human endometrial (uterine) epithelial cells (served as controls). Then, SIRT2 overexpression plasmids (constructed with pcDNA3.1 vector) and knock-down plasmids (constructed with pGPH1 vector) were transfected in Ishikawa cells and KLE cells, respectively to assess the influence of SIRT2 on EC cell stemness and chemosensitivity to cisplatin and paclitaxel. RESULTS: SIRT2 mRNA and protein were both overexpressed in EC cell lines (including Ishikawa cells, AN3CA cells, HEC1A cells, and KLE cells) compared with controls. Upregulation of SIRT2 increased the sphere formation capacity (by sphere formation assay and extreme limiting dilution analysis) and CD133+ cells rate in Ishikawa cells, whereas knock-down of SIRT2 reduced the sphere formation capacity and CD133+ cells rate in KLE cells. As for chemosensitivity, upregulation of SIRT2 increased relative cell viability in cisplatin-treated and paclitaxel-treated Ishikawa cells. In contrast, SIRT2 knock-down suppressed relative cell viability in cisplatin-treated but not in paclitaxel-treated KLE cells. In addition, SIRT2 overexpression increased, while SIRT2 knock-down reduced p-MEK and p-ERK1/2 levels in EC cells. CONCLUSION: SIRT2 promotes cell stemness and activates the MEK/ERK signaling pathway while represses chemosensitivity in EC.

MicroRNA­126 protects SH­SY5Y cells from ischemia/reperfusion injury­induced apoptosis by inhibiting RAB3IP.

MicroRNA (miR)­126 is known to inhibit inflammatory responses in various inflammatory­related diseases, but its role during the cerebral ischemia/reperfusion (I/R) injury remains unknown. The present study aimed to examine the interaction between miR­126 and RAB3A interacting protein (RAB3IP), and explore its potential protective effects during I/R injury. The human neuroblastoma cell line SH­SY5Y was cultured in an oxygen­glucose deprivation/reoxygenation (OGD/R) environment to simulate I/R injury to assess miR­126 expression and cell viability. SH­SY5Y cells cultured in normal conditions were used as a negative control (NC) group. SH­SY5Y cells were transfected with a miR­126 mimic or an NC mimic, then cultured in OGD/R conditions; in rescue experiments, SH­SY5Y cells were co­transfected with RAB3IP overexpression or NC plasmid together with mimic­NC or mimic­miR, and then maintained in an OGD/R environment to evaluate miR­126, RAB3IP expression, cell viability and apoptosis. Cell viability was reduced in the Model group compared with the NC group, suggesting the successful construction of the OGD/R model. miR­126 expression was downregulated in the Model group compared with the NC group. However, following transfection with mimic­miR, cell viability increased compared with the mimic­NC group. Annexin V and PI staining and Hoechst/PI assays also indicated that apoptosis was reduced in the mimic­miR group compared with the mimic­NC group. RAB3IP expression was reduced following mimic­miR transfection. In rescue experiments, miR­126 negatively regulated RAB3IP expression; by contrast, RAB3IP did not affect that of miR­126. In addition, RAB3IP overexpression attenuated the protective effect of miR­126 on OGD/R­induced apoptosis. These findings suggest that miR­126 protects against cerebral I/R injury by targeting RAB3IP.

MicroRNA­199a­3p inhibits ovarian cancer cell viability by targeting the oncogene YAP1.

MicroRNA­199a­3p (miR­199a­3p) is aberrantly expressed in various types of cancer where it exhibits a tumor suppressive role. However, the biological role of miR­199a­3p in ovarian cancer (OC) remains unclear. The present study aimed to investigate whether miR­199a­3p was a tumor suppressor in OC and to identify the possible mechanisms. It was found that miR­199a­3p expression was significantly downregulated in the tumor tissues and blood samples of patients with OC, as well as in three OC cell lines. In addition, its low expression was closely associated with International Federation of Gynecology and Obstetrics disease stage, histological grade and lymph node metastasis. It was demonstrated that overexpression of miR­199a­3p inhibited the viability and promoted apoptosis of OV90 and SKOV­3 cells. In addition, Yes­associated protein 1 (YAP1), a well­known oncogene, was identified as a direct target of miR­199a­3p in OC cells. Additionally, it was observed that YAP1 was significantly increased and inversely correlated with miR­199a­3p expression in OC tissues. Notably, YAP1 overexpression abrogated the tumor suppressive effects of miR­199a­3p in vitro. Collectively, the present results indicated that miR­199a­3p suppressed viability in OC cells, at least partly via inhibiting the YAP1 oncogene, suggesting that miR­199a­3p may act as a biomarker and therapeutic target for patients with OC.

Higher Levels of Triglyceride, Fatty Acid Translocase, and Toll-Like Receptor 4 and Lower Level of HDL-C in Pregnant Women with GDM and Their Close Correlation with Neonatal Weight.

OBJECTIVES: In this study, we aimed to compare the levels of maternal blood lipids, placental and venous blood lipid transporters, and inflammatory factor receptors in pregnant women with and without gestational diabetes mellitus (GDM). We also aimed to figure out the relationship between these values and neonatal weight. METHODS: Fifty pregnant women with GDM under blood glucose control belong to the case group, and 50 pregnant women with normal glucose tolerance in concurrent delivery belong to the control group. Fasting venous blood of these pregnant women was taken 2 weeks before delivery, and umbilical cord blood was collected after delivery. The levels of triglyceride (TG), serum total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (HDL-C) in maternal blood and umbilical cord blood were tested in the laboratory department of our hospital. The level of toll-like receptor 4 (TLR4) in serum of umbilical veins was detected by the double-antibody sandwich ELISA. Western blot and RT-PCR were used to detect the protein and mRNA expressions of TLR4, LPL, and FAT/CD36 in the placenta. RESULTS: The level of TG in maternal blood in the case group was remarkably higher than that in the control group, which was opposite to the level of HDL-C. In the umbilical cord blood of women with GDM, the expression of TLR4 increased and was closely correlated with neonatal weight. In the placenta of women with GDM, the expressions of FAT/CD36 and TLR4 increased, and both of them were closely correlated with neonatal weight. Besides, TLR4 in umbilical cord blood increased and was closely correlated with neonatal weight. Although the expression of LPL in the placenta decreased, it had no obvious correlation with neonatal weight. CONCLUSIONS: TG in maternal blood, TLR4 in the placenta and umbilical cord blood, and FAT/CD36 in the placenta were positively correlated with neonatal weight. However, HDL-C in maternal blood was negatively correlated with neonatal weight. Although the expression of LPL in the placenta reduced due to GDM, it had no correlation with neonatal weight.

Sirtuin 2 in Endometrial Cancer: A Potential Regulator for Cell Proliferation, Apoptosis and RAS/ERK Pathway.

OBJECTIVE: The present study aimed to explore the function of sirtuin 2 (SIRT2) on cell proliferation, apoptosis, rat sarcoma virus (RAS)/ extracellular signal-regulated kinase (ERK) pathway in endometrial cancer (EC). METHODS: SIRT2 expression in human EC cell lines and human endometrial (uterine) epithelial cell (HEEC) line was assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot. SIRT2 knock-down and control knock-down plasmids were transfected into HEC1A cells, respectively; SIRT2 overexpression and control overexpression plasmids were transfected into Ishikawa cells, respectively. After transfection, SIRT2, HRas proto-oncogene, GTPase (HRAS) expressions were evaluated by RT-qPCR and western blot. ERK and phosphorylated ERK (pERK) expressions were evaluated by western blot. Meanwhile, cell proliferation and cell apoptosis were measured. RESULTS: Compared to normal HEEC cell line, SIRT2 mRNA and protein expressions were increased in most human EC cell lines (including HEC1A, RL952 and AN3CA), while were similar in Ishikawa cell line. In HEC1A cells, SIRT2 knock-down decreased cell proliferation but increased apoptosis. In Ishikawa cells, SIRT2 overexpression induced cell proliferation but inhibited apoptosis. For RAS/ERK pathway, SIRT2 knock-down reduced HRAS and inactivated pERK in HEC1A cells, whereas SIRT2 overexpression increased HRAS and activated pERK in Ishikawa cells, suggesting that SIRT2 was implicated in the regulation of RAS/ERK pathway in EC cells. CONCLUSION: SIRT2 contributes to the EC tumorigenesis, which appears as a potential therapeutic target.

MicroRNA-199a-5p suppresses the cell growth of colorectal cancer by targeting oncogene Caprin1.

MicroRNAs-199a-5p (miR-199a-5p) plays critical regulatory roles in various types of human cancers. However, the biological function and regulatory mechanisms of miR-199a-5p in colorectal cancer (CRC) remain unclear. The aim of this study was to investigate the role of miR-199a-5p in CRC and possible mechanisms of its action. The expression of miR-199a-5p in CRC tumor tissues was validated using quantitative real-time PCR (qRT-PCR). The effects of miR-199a-5p on cell proliferation and apoptosis were evaluated in vitro. Then, the association of miR-199a-5p and its downstream target was investigated in both cell line and clinical specimens. Furthermore, gain- and loss-of-function studies of cytoplasmic activation/proliferation-associated protein-1 (Caprin1) were performed to assess whether the suppressive effect of on CRC cells were via targeting Caprin1. Using a microarray platform, we focused on miR-199a-5p for further research, which was one of the most markedly downregulated miRNAs in CRC tumor tissues. Functionally, the overexpression of miR-199a-5p inhibited proliferation and induced apoptosis in both HTC116 and SW480 cells. Furthermore, cytoplasmic activation/proliferation-associated protein-1 (Caprin1), a well-known oncogene, was directly targeted by miR-199a-5p. It was also observed that Caprin1 was upregulated, and inversely correlated with miR-199a-5p levels in CRC tissues. Further investigations revealed that knockdown of Caprin1 by siRNA has similar role with miR-199a-5p overexpression in CRC cells, suggesting the oncogenic role of Caprin1 in CRC. In the contrast, we found that overexpression of Caprin1 reversed the suppressive effects of miR-199a-5p on CRC cells. Collectively, our study suggests that miR-199a-5p/Caprin1 axis may serve as potential therapeutic targets for the treatment of CRC.

Eukaryotic initiation factor 3B is overexpressed and correlates with larger tumor size, advanced FIGO stage, and shorter overall survival in epithelial ovarian cancer patients.

BACKGROUND: This study aimed to detect the eukaryotic initiation factor 3B (EIF3B) expression and explore its correlation with clinical features and prognosis in epithelial ovarian cancer (EOC) patients. METHODS: A total of 230 primary EOC patients underwent surgery treatment were retrospectively reviewed. Immunohistochemical (IHC) assay was used to determine EIF3B expression in tumor and adjacent tissue specimens of all patients. According to the total IHC score, the expression of EIF3B was classified as low expression and high expression, and the latter was further divided into 3 grades: high+, high++, and high+++ expressions. Overall survival (OS) was calculated. RESULTS: Eukaryotic initiation factor 3B expression was increased in tumor tissue compared with adjacent tissue. Tumor EIF3B high expression correlated with larger tumor size (>10 cm), lymphatic metastasis, and advanced International Federation of Gynecology and Obstetrics stage (FIGO) (III/IV). Besides, OS was decreased in patients with tumor EIF3B high expression compared with patients with tumor EIF3B low expression, and further analysis showed that the OS was shortest in patients with tumor EIF3B high+++ expression, followed by patients with tumor EIF3B high++ expression and patients with tumor EIF3B high + expression, and the longest in patients with tumor EIF3B low expression. Additionally, higher tumor EIF3B expression, peritoneal cytology (positive), ascites volume (>100 mL), differentiation (poor vs. well/moderate), tumor size (>10 cm), FIGO stage (III/IV vs. I/II), and cancer antigen 125 (>1000 U/mL) independently predicted shorter OS. CONCLUSION: Eukaryotic initiation factor 3B exhibits a clinical value for monitoring disease progression and predicting prognosis in EOC patients.

Ocean variability and air-sea fluxes produced by atmospheric rivers.

Atmospheric rivers (ARs) cause heavy precipitation and flooding in the coastal areas of many mid-latitude continents, and thus the atmospheric processes associated with the AR have been intensively studied in recent years. However, AR-associated ocean variability and air-sea fluxes have received little attention because of the lack of high-resolution ocean data until recently. Here we demonstrate that typical ARs can generate strong upper ocean response and substantial air-sea fluxes using a high-resolution (1/12°) ocean reanalysis. AR events observed during the CalWater 2015 field campaign generate large-scale on-shore currents that hit the coast, generating strong narrow northward jets along the west coast of North America, in association with a substantial rise of sea level at the coast. In the open ocean, the AR generates prominent changes of mixed layer depth, especially south of 30°N due to the strong surface winds and air-sea heat fluxes. The prominent cooling of SST is observed only in the vicinity of AR upstream areas primarily due to the large latent heat flux. Using a long-term AR dataset, composite structure and variations of upper ocean and air-sea fluxes are presented, which are consistent with those found in the events during CalWater 2015.