Identification and validation of oxeiptosis-associated lncRNAs and prognosis-related signature genes to predict the immune status in uterine corpus endometrial carcinoma.

As a novel cell death modality, oxeiptosis is mainly caused by oxidative stress. However, the associations of uterine corpus endometrial carcinoma (UCEC) with oxeiptosis-associated long non-coding RNAs (lncRNAs) are unknown. Here, to identify hub oxeiptosis-associated lncRNAs in UCEC, we collected the data for lncRNAs and gene expression in UCEC from The Cancer Genome Atlas (TCGA) database. Then, a lncRNA risk signature was constructed, and its prognostic value was further evaluated. Finally, the expression levels of hub lncRNA HOXB-AS3 were validated by quantitative RT-PCR analysis. MTT and wounding analyses were also applied to confirm the role of HOXB-AS3 knockdown on UCEC cells. Five lncRNAs associated with oxeiptosis and connected to the prognosis of UCEC were identified, and a risk signature was constructed based on these identified lncRNAs. Our clinical value analyses suggested that the risk signature was closely connected to the overall survival, TNM stage, and grade of UCEC patients. Meanwhile, compared to the conventional clinicopathological characteristics, this risk signature exhibited significantly higher diagnostic accuracy. Moreover, the potential mechanism analysis indicated a close connection of this risk signature to tumor stemness, m6A-related genes, immune cell infiltration, and immune subtypes. Based on the risk scores, we constructed a nomogram. In vitro experiments found that HOXB-AS3 was significantly higher expressed in UCEC cells, and the silence of HOXB-AS3 inhibited the proliferation and migration of UCEC cells. In conclusion, using five hub lncRNAs associated with oxeiptosis, we generated a risk signature, which could be applied in the novel therapeutic strategies of UCEC development.

Identification of an endoplasmic reticulum stress-associated gene signature to predict the immune status and prognosis of cutaneous melanoma.

Besides protecting normal cells from various internal and external perturbations, endoplasmic reticulum (ER) stress is also directly related to the pathogenesis of cutaneous melanoma (CM). However, due to the lack of specific molecular biomarkers, ER stress has not been considered a novel treatment target for CM. Here, we identified ER stress-related genes involved in the prognosis of CM patients and constructed an effective model for the prognostic prediction of these patients. First, gene expression data of CM and normal skin tissues from the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases were retrieved to identify differentially expressed ER stress-related genes in CM. Meanwhile, an independent cohort obtained from the Gene Expression Omnibus (GEO) database was used for validation. The ER stress genes (ZBP1, DIABLO, GNLY, FASLG, AURKA, TNFRSF21, and CD40LG) that were associated with CM prognosis were incorporated into our prognostic model. The functional analyses indicated that the prognostic model was correlated with patient survival, gender, and cancer growth. Multivariate and univariate Cox regressions revealed that the constructed model could serve as an independent prognostic factor for CM patients. The pathway enrichment analysis showed that the risk model was enriched in different immunity and cancer progression-associated pathways. Moreover, the signature model was significantly connected with the immune subtypes, infiltration of immune cells, immune microenvironment, as well as tumor stem cells. The gene function analysis revealed that 7 ER stress genes were differentially expressed in CM patients and were significantly associated with prognosis and several antitumor drugs. Overall, our current model presented predictive value for the prognosis of CM patients and can be further used in the development of novel therapeutic strategies for CM.

Downregulation of peroxiredoxin II suppresses the proliferation and metastasis of gastric cancer cells.

Peroxiredoxin (Prx) II is an imperative member of the superfamily of peroxidases. It serves an essential role in scavenging organic hydroperoxide and H2O2. It is involved in the development of various malignant tumors. In order to investigate the significance of Prx II expressions level in gastric cancer (GC), downregulation of Prx II was performed to investigate its role in the proliferation and migration of gastric adenocarcinoma cells. In GC cells and 45 GC specimens, the mRNA and protein expression levels of Prx II were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. The Prx II expression profile in another 116 GC specimens was also detected with immunohistochemistry (IHC). The changes in the proliferation and migration of MKN45 and MGC-803 cells folllowing transfection with small interfering RNA (siRNA) were detected by cell counting kit (CCK)-8, western blot analysis, and Transwell migration and invasion assays. The results revealed that the expression of Prx II in GC tissues and GC cells were significantly upregulated compared with the normal control. There was a significant association between the expression level of Prx II and various factors, including tumor size, histological differentiation, the depth of invasion, the stage of tumor-node-metastasis (TNM) and lymph node metastasis in GC (P<0.05). Survival in patients with higher Prx II expression was significantly decreased compared with those with lower Prx II expression (P<0.01). Prx II, depth of invasion, lymph node metastasis and distant metastasis were identified as independent prognosis factors of GC (P<0.05). Knockdown of Prx II significantly suppressed the proliferation and the migration of GC cells. These experiments revealed that Prx II promotes the development of GC, affecting the survival of patients with GC.

Hypoxia stimulates invasion and migration of human cervical cancer cell lines HeLa/SiHa through the Rab11 trafficking of integrin αvß3/FAK/PI3K pathway-mediated Rac1 activation.

Hypoxia plays a key role in tumour cell survival, invasion, and metastasis. An increasing number of studies have attempted to characterize the tumour response to hypoxia and to identify predictive markers of disease. Here we show that hypoxia increases tumour cell invasion and migration by the modulation of Rab11, an important molecule for vesicular trafficking. In our study, we found that Rab11, together with the activation of Rac1, could stimulate invasion and migration of cervical cancer cell lines HeLa/SiHa in hypoxia. Activation of Rac1 activity by hypoxia seems to be central to carcinoma invasion. We also found that these effects could be related to the integrin αvß3. In addition, we studied the molecular pathway for this process. Our results showed that in cervical cancer cell lines HeLa/SiHa, Rac1 activation in hypoxia could stimulate invasion and migration, and this process was mediated by integrin αvß3-mediated FAK and PI3K phosphorylation. Furthermore, hypoxia induced a dramatic increase in αvß3 integrin surface expression, and this increase is dependent on Rab11. In conclusion, our study might provide a new mechanism for the effect of hypoxia on stimulating cervical carcinoma invasion.