Aldo-keto reductase family member C3(AKR1C3)promotes hepatocellular carcinoma cell growth by producing prostaglandin F2α

Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chemotherapy.Therefore,new therapeutic targets are needed.We analyzed gene expression profiles between HCC tissues and normal adjacent tissues from public databases and found that the expression of genes involved in lipid metabolism was significantly different.The analysis showed that AKR1C3 was upregulated in tumors,and high AKR1C3 expression was associated with a poorer prognosis in HCC patients.In vitro,assays demonstrated that the knockdown of AKR1C3 or the addition of the AKR1C3 inhibitor indomethacin suppressed the growth and colony formation of HCC cell lines.Knockdown of AKR1C3 in Huh7 cells reduced tumor growth in vivo.To explore the mechanism,we performed pathway enrichment analysis,and the results linked the expression of AKR1C3 with prostaglandin F2 alpha(PGF2a)downstream target genes.Suppression of AKR1C3 activity reduced the production of PGF2a,and supplementation with PGF2a restored the growth of indomethacin-treated Huh7 cells.Knockdown of the PGF receptor(PTGFR)and treatment with a PTGFR inhibitor significantly reduced HCC growth.We showed that indomethacin potentiated the sensitivity of Huh7 cells to sorafenib.In summary,our results indicate that AKR1C3 upregulation may promote HCC growth by promoting the production of PGF2α,and suppression of PTGFR limited HCC growth.Therefore,targeting the AKR1C3-PGF2a-PTGFR axis may be a new strategy for the treatment of HCC.

Liver collision tumor of primary hepatocellular carcinoma and neuroendocrine carcinoma:A rare case report

BACKGROUND Hepatocellular carcinoma(HCC)can occasionally develop with other non-HCC cell types,either in a combined type or collision type.A collision tumor is defined as two histopathologically distinct tumors of the same organ lacking a clear transition zone.Hepatic collision tumors are rare.Among them,“hepatocellular carcinoma-hepatic neuroendocrine carcinoma”(HCC-NEC)collision tumors are especially rare and information about them is rarely published.CASE SUMMARY A 48-year-old man with typical findings of HCC underwent consecutive therapies,including radiofrequency ablation and embolization prior to resection.Diagnosis of the HCC-NEC collision tumor in the right liver and another HCC in the left liver was established following surgical resection.The patient displayed NEC metastasis following resection and succumbed to septicemia after 2 more rounds of chemotherapy.To our knowledge,this is the 25th reported case of mixed HCC-NEC tumor.The rarity of HCC-NEC collision tumors and the absence of diagnostic criteria make it difficult to differentiate this condition from simple liver tumors,especially in patients with chronic liver disease.CONCLUSION Our case highlights the difficulty in accurately diagnosing HCC-NEC in the absence of histological evidence.The prognosis is poor for this condition,although ultrasound-guided liver biopsy can be helpful to establish a prompt diagnosis.Further accumulation of such cases could help establish an accurate diagnosis earlier.Early discovery of NEC may allow for better treatment strategies and better prognoses.