Circular RNA PRKCI (hsa_circ_0067934): a potential target in the pathogenesis of human malignancies.

Circular RNAs (circRNAs) are a new type of endogenous non-coding RNA formed by a covalent closed loop. CircRNAs are characterized by specificity, universality, conservation, and stability. They are abundant in eukaryotic cells and have biological regulatory roles at various transcriptional and post-transcriptional levels. The upregulation of circPRKCI has been observed in a variety of tumors and is directly related to the clinicopathological characteristics of tumors and prognosis. More importantly, circPRKCI can participate in the tumorigenesis, progression, recurrence, and metastasis of various tumors through many functional mechanisms, including the activation of signaling pathways, such as the phosphatidylinositol-3-kinase (PI3K)/AKT pathway, and sponging of many microRNAs (miRNAs). This review summarizes the progress achieved in understanding the biological functions of circRNA PRKCI in various tumors. The goal is to inform the discovery of more functional mechanisms and new anticancer molecular targets.

Prognostic Signature GXYLT2 Is Correlated with Immune Infiltration in Bladder Cancer.

Background: GXYLT2 (glucoside xylosyltransferase 2) was known as an important gene that regulates classical Notch signaling and is involved in progression in human tumors. However, the correlation between GXYLT2 expression and bladder cancer remains unclear. Methods: GXYLT2 expression was analyzed by ONCOMINE database, GEPIA database, and TIMER database. The Cancer Genome Atlas (TCGA) was utilized to confirm relationships between GXYLT2 and molecular subtypes of BLCA (bladder cancer). We discovered prognostic value of GXYLT2 in BLCA using GEPIA, LinkedOmics database, and Kaplan-Meier Plotter database. Subsequently, correlations between GXYLT2 and tumor immune infiltration were investigated through TIMER and TISIDB website. We then downloaded data of patients with BLCA from TCGA website, to conduct functional annotations and to construct protein-protein interaction network through STRING and Enrich web servers. Results: Significant differences were observed between GXYLT2 expression of bladder cancer and normal tissues. GXYLT2 was a poor prognostic biomarker in BLCA with impact on diverse clinical characteristics. We found that GXYLT2 was closely related to tumor immune infiltrated cells and immune genes. Functional annotations indicated that GXYLT2 was linked to immune-related pathways. Conclusions: The results suggested that GXYLT2 was associated with a poor prognosis and tumor immune cell infiltration of BLCA. GXYLT2 could be a promising therapeutic target in bladder cancer.

TSPAN31 regulates the proliferation, migration, and apoptosis of gastric cancer cells through the METTL1/CCT2 pathway.

Gastric cancer (GC) is one of the most common human malignancies worldwide, but the molecular mechanism of GC has not been fully elucidated. Tetraspanin 31 (TSPAN31) has been rarely studied in human malignant tumors. This study aimed to investigate the effects of TSPAN31 on GC. We analyzed GC tissues through high-throughput sequencing technology and chose TSPAN31 with high expression. The expression of TSPAN31 in GC was analyzed through bioinformatics website and qRT-PCR. The protein level of TSPAN31 in GC tissues was determined by western blot and immunochemistry. The proliferation, migration, and apoptosis of GC cells were detected by the cell counting kit-8, transwell, and apoptosis experiments. METTL1 and CCT2 that may co-express with TSPAN31 were predicted by the GEPIA database, and analyzed the correlation between the expression levels of TSPAN31, METTL1 and CCT2. The results shows TSPAN31 was highly expressed in GC tissues, and high expression of TSPAN31 was found to result in poor prognosis of patients with GC. TSPAN31 could regulate the proliferation, migration and apoptosis of GC cells. The relative expression levels of TSPAN31, METTL1 and CCT2 in GC were positively correlated. Low expression of TSPAN31 could partially reverse the effect of high expression of METTL1 and CCT2 on the tumor progression of GC cells. In conclusion, TSPAN31 was highly expressed in GC tissues and led to poor prognosis of patients with GC. TSPAN31 may regulate the proliferation, migration, and apoptosis of GC cells. This regulatory mechanism may be achieved through co-expression with METTL1 and CCT2.

RCN1 induces sorafenib resistance and malignancy in hepatocellular carcinoma by activating c-MYC signaling via the IRE1α-XBP1s pathway.

The increasing incidence of hepatocellular carcinoma (HCC) is of great concern globally, but the molecular pathogenesis of these tumors remains unclear. Sorafenib is a first-line drug for the treatment of advanced HCC. However, the efficacy of sorafenib in improving patient survival is limited, and most patients inevitably develop resistance to this drug. Recent studies have demonstrated that the activation of the IRE1α-XBP1s pathway might play a protective role in the response to sorafenib and contribute to malignancy in HCC. Here, we found that RCN1, an endoplasmic reticulum resident protein, is significantly upregulated in sorafenib-resistant HCC cells and promotes tumor progression. Our analysis showed that RCN1 may be an independent predictor of tumor recurrence and overall survival. Mechanistically, RCN1 promotes the dissociation of GRP78 from IRE1α in sorafenib-resistant cells by interacting with GRP78 through its EFh1/2 domain. Subsequently, the IRE1α-XBP1s pathway, a branch of the unfolded protein response, is sustainably activated. Interestingly, IRE1α-XBP1s pathway activity is required for c-MYC signaling, one of the most highly activated oncogenic pathways in HCC. These results suggest that RCN1-targeted therapy might be a feasible strategy for the treatment of HCC.