Abstract
Hepatocellular carcinoma (HCC), which accounts for 85–90% of primary liver cancer, is now the second leading cause of cancer-related mortality worldwide. Here we reported that Aldo-Keto Reductase family 7A isoform 3 (AKR7A3) is frequently down-regulated in HCC, associating with poor overall survival rate, elevated serum α-fetoprotein (AFP) and poor differentiation of HCC. The promoter region of AKR7A3 was detected to be hypermethylated. Loss of heterozygosity (LOH) was also detected in AKR7A3. Functional assays on both AKR7A3 overexpressed and knockdown cells, including foci formation, colony formation in soft agar, migration, invasion and tumor formation in nude mice, demonstrated the strong tumor suppressive functions of AKR7A3. In addition, treatment of chemotherapy drug cisplatin showed that AKR7A3 sensitizes tumor cells to apoptosis. Mechanistically, western blot analysis showed that overexpression of AKR7A3 inhibits the activation of ERK, c-Jun and NF-κB. In summary, we found that AKR7A3 functions as a tumor suppressor gene in HCC through attenuating c-Jun, ERK and NF-κB signaling pathways.
Highlights
Hepatocellular carcinoma (HCC) is one of the most frequently diagnosed malignancies with poor prognosis [1]
Sequencing data revealed that Aldo-Keto Reductase family 7A isoform 3 (AKR7A3) was among the 102 genes that were down-regulated in all the 3 HCC samples, as compared to paired non-tumor samples
To detect the expression level of AKR7A3 in a larger cohort of HCC samples, qRT-PCR was performed on 129 pairs of HCC patient samples
Summary
Hepatocellular carcinoma (HCC) is one of the most frequently diagnosed malignancies with poor prognosis [1]. Aldo-Keto Reductase Family 7, Member A3 (AKR7A3), which locates on chromosome 1p36, belongs to the aldo-keto reductases (AKRs) superfamily. This super family consists of 15 families with more than 140 members, which function to reduce aldehydes and ketones to alcohols [6]. These enzymes were reported to play important roles in nuclear receptor signaling, cellular metabolism, inflammatory responses, osmoregulation, endobiotic and xenobiotic detoxification and hormone synthesis [6,7]. High expression level of AKR7A3 significantly associates with longer disease free survival [10]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
