BackgroundMalignant pheochromocytoma/paraganglioma (PCPG) is lethal and difficult to diagnose before metastasis. This study is aiming to characterize the PCPG and explore novel prognostic markers.MethodsClinical data of patients with pathologically confirmed invasive and noninvasive PCPG were collected and analyzed. Then, the differentially expressed genes (DEGs) and HUB genes were identified by R package “limma” in GSE67066‐GPL570. Afterward, the prognostic markers were screened out using R packages of “survival” and “survminer” based on the TCGA data.ResultsThe 34 invasive PCPGs were characterized by irregular contour and unclear boundary on CT and capsule/extracapsule tissue invasion on pathology compared with the 42 noninvasive PCPGs. Then, 29 upregulated and 30 downregulated DEGs were identified in malignant PCPG compared with benign, which were mainly enriched in the terms of calcium ion binding, neuron cell–cell adhesion, axon, regulation of hormone levels, and regulation of secretion by cell. Of which, nine DEGs were furtherly selected as the HUB genes. Finally, CNTN4 and SH3GL2 were found to be highly expressed in malignant PCPGs and negatively correlated with progression‐free interval.ConclusionsMalignant PCPGs tend to be aggressive in imaging and pathology. The high expression of CNTN4 and SH3GL2 in PCPGs may indicate a poor prognosis.

This study was designed to explore the effects of exosomal miR‐421 secreted by cancer‐associated fibroblasts (CAFs) on pancreatic cancer (PC) progression and the mechanisms involved. CAFs and exosomes (exos) were isolated and identified. PC cells were treated with CAF‐derived exos (CAF‐exos). Western blotting and quantitative polymerase chain reaction (qPCR) were used to measure miR‐421, sirtuin‐3 (SIRT3), and hypoxia duciblefactors‐1 alpha (HIF‐1α) levels. Cell counting kit‐8 (CCK‐8), wound‐healing, and transwell migration assays were used to measure proliferation, migration, and invasion abilities of the cells. Dual‐luciferase assay and RNA immunoprecipitation (RIP) experiment analyzed the relationship between miR‐421 and SIRT3. Chromatin immunoprecipitation (f)‐verified H3K9Ac enrichment in the HIF‐1α promoter region. In vivo tumorigenesis experiments were performed to further explore the effects of exosomal miR‐421 from CAFs on PC. CAFs and exos were successfully isolated. CAF‐exo‐treated PC cells highly expressed miR‐421 and had increased cell proliferation, migration, and invasion abilities. Knocking down miR‐421 increased the expression of SIRT3. SIRT3 is a target of miR‐421, and inhibiting the expression of SIRT3 reversed the negative effects of miR‐421 knockdown on PC cell. Knocking down miR‐421 in CAF‐exo inhibited the expression of HIF‐1α in PC cells. Moreover, SIRT3‐mediated HIF‐1α expression by regulating H3K9Ac. HIF‐1α overexpression reversed the inhibiting effects of SIRT3 overexpression on PC progression and counteracted the inhibiting effects of miR‐421 knockdown on glycolysis. Moreover, in vivo tumorigenesis experiments showed that knocking down miR‐421 attenuated CAF‐exo induced tumor growth. Exosomal miR‐421 from CAFs promoted PC progression by regulating the SIRT3/H3K9Ac/HIF‐1α axis. This study provided insights into the molecular mechanism of PC.

Pancreatic cancer (PC) is a common malignant cancer characterized by high mortality and poor prognosis. LINC00690 was involved in the occurrence and progression of PC, but the underlying mechanisms require further investigation. The goal of this study was to figure out how LINC00960 mediates glycolysis in PC. LINC00960, miR-326-3p, and Tuftelin 1 (TUFT1) expression levels were detected in PC cell lines.LINC00960 and TUFT1 expression levels were increased in PC cells when compared with normal pancreatic cells, whereas miR-326-3p expression levels were decreased.The expression levels of LINC00690 affected glycolysis in PC, and inhibition of LINC00960 inhibited tumor growth in vivo. LINC00690 targeted and suppressed the expression of miR-326-3p. MiR-326-3p bound to TUFT1, and miR-326-3p inhibited AKT-mTOR pathway activation via TUFT1. In conclusion, the depletion of LINC00960 repressed cell proliferation and glycolysis in PC by mediating the miR-326-3p/TUFT1/AKT-mTOR axis. Thus, we present a novel mechanism underlying the progression of PC that suggests LINC00960 is a potential therapeutic target for this cancer.

The mortality rate of pancreatic cancer (PC) remains high due to late diagnosis, early metastasis, and difficulty of complete resection. The online databases showed that potassium voltage-gated channel subfamily H member 2 (KCNH2) was highly expressed in pancreatic tumor tissues and was closely related to the poor survival of patients with PC. However, the mechanism of action of KCNH2 in PC is still unclear. In the present study, for the first time, we explored the regulatory effect of KCNH2 in PC. The results showed that KCNH2 was upregulated in PC compared with normal pancreatic tissues. High KCNH2 expression was associated with low tissue differentiation, high malignancy, and poor prognosis of PC. Moreover, knockdown of KCNH2 inhibited the proliferation and apoptosis of PC cells, as well as the epithelial-mesenchymal transition process, thereby promoting PC cell migration and invasion. In addition, KCNH2 knockdown inhibited the progression and metastasis of PC in a mouse xenograft model. In conclusion, these findings highlighted the potential of KCNH2 as a targeted molecule in the treatment of PC.