Functional genetic variant of <i>HSD17B12</i> in the fatty acid biosynthesis pathway predicts the outcome of colorectal cancer

Lin, Yongcheng; Meng, Yujie; Zhang, Jinying; Ma, Ling; Jiang, Lu; Zhang, Yi; Yuan, Man; Ren, An‐Jing; Zhu, Weiyou; Li, Shuwei; Shu, Yongqian; Du, Mulong; Zhu, Lingjun

doi:10.1111/jcmm.16026

Cited by 6 publications

(6 citation statements)

References 54 publications

(91 reference statements)

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“… (Mokhtari et al 2022 ) Increased risk of death and progression of colorectal cancer in patients with 10838164 C>T genetic variant was reported, which was correlated with increased transcriptional activity and upregulation of HSD17B12. (Lin et al 2020 ) …”

Section: Enzymes Involved In Vl-pupa Synthesis In Crcmentioning

confidence: 99%

“…Higher expression of HSD17B12 was detected in colorectal tumor tissues, suggesting a possible correlation between its activity and CRC. Functional genetic variants of HSD17B12 are correlated with the outcome of CRC (Lin et al 2020 ). A Cox regression model that evaluated the genetic effects on CRC overall survival and progression-free survival revealed that rs10838164 C>T in HSD17B12 was significantly associated with an increased risk of CRC progression and death.…”

Section: Enzymes Involved In Vl-pupa Synthesis In Crcmentioning

confidence: 99%

“…A Cox regression model that evaluated the genetic effects on CRC overall survival and progression-free survival revealed that rs10838164 C>T in HSD17B12 was significantly associated with an increased risk of CRC progression and death. The T allele can increase HSD17B12 expression by enhancing the binding affinity of transcription factors to promote the transcriptional activity of the HSD17B12 gene (Lin et al 2020 ).…”

Section: Enzymes Involved In Vl-pupa Synthesis In Crcmentioning

confidence: 99%

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Emerging roles of polyunsaturated fatty acid synthesis pathway in colorectal cancer

Moon

2023

Animal Cells and Systems

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The development of colorectal cancer typically involves the accumulated influences of genetic alterations, medical issues, lifestyle, and diet. Dietary fatty acids appear to affect the tumorigenesis and progression of colorectal cancer. Despite conflicting results, the current consensus on the effects of very long-chain polyunsaturated fatty acids on colorectal cancer is that low levels of eicosapentaenoic acid and docosahexaenoic acid, and high levels of arachidonic acid are associated with an increased risk of colorectal cancer. Altered levels of arachidonic acid in membrane phospholipids can change the levels of prostaglandin E 2 , which affect the biological activities of cancer cells in multiple stages. Arachidonic acid and other very long-chain polyunsaturated fatty acids can affect tumorigenesis in prostaglandin E 2 -independent manners as well, including stabilization of β-catenine, ferroptosis, ROS generation, regulation of transcription factors, and de novo lipogenesis. Recent studies have revealed an association between the activities of enzymes synthesizing very long-chain polyunsaturated fatty acids and tumorigenesis and cancer progression, although the mechanisms are still unknown. In this study, PUFA effects on tumorigenesis, the endogenous very long-chain polyunsaturated fatty acid synthesis pathway, metabolites of arachidonic acid and their effects on tumorigenesis and progression of CRC, and current knowledge that supports the association of the enzymes involved in the polyunsaturated fatty acid synthesis pathway with colorectal cancer tumorigenesis and progression are reviewed.

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Section: Enzymes Involved In Vl-pupa Synthesis In Crcmentioning

confidence: 99%

Section: Enzymes Involved In Vl-pupa Synthesis In Crcmentioning

confidence: 99%

Section: Enzymes Involved In Vl-pupa Synthesis In Crcmentioning

confidence: 99%

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Emerging roles of polyunsaturated fatty acid synthesis pathway in colorectal cancer

Moon

2023

Animal Cells and Systems

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“…Given that complete knockout of the Hsd17B12 gene is lethal during gestation in mice (Rantakari et al, 2010), and many animals homozygous for the G at this SNP were present in the population, it is highly unlikely that this variation results in a nonfunctional protein. Various approaches have also associated variation in the HSD17B12 gene with obesity and type 2 diabetes (Hachim et al, 2020), longissimus muscle area (Medeiros de Oliveira Silva et al, 2017), and cancer outcome (Sun et al, 2011;Dai et al, 2019;Lin et al, 2020). One study identified transcriptional regulation as a potential functional effect of a SNP found in the region of the HSD17B12 gene in humans that was associated with obesity and type 2 diabetes (Hachim et al, 2020), but the functional significance of other identified SNP has not been delineated.…”

Section: Discussionmentioning

confidence: 99%

Relationships between prostaglandin concentrations, a single nucleotide polymorphism in HSD17B12, and reproductive performance in dairy cows

Juengel

Mosaad

Mitchell

et al. 2022

Journal of Dairy Science

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Prostaglandins are involved in multiple processes important for fertility, with previous work in mice highlighting a potential role for the HSD17B12 gene in prostaglandin biosynthesis. This study aimed to determine the associations among circulating prostaglandin concentrations, a missense SNP in the HSD17B12 gene predicted to disrupt protein function, and fertility traits in first-lactation Holstein-Friesian dairy cows. We used a study population of approximately 500 animals specifically bred to have either a positive (POS, +5%) or negative (NEG, −5%) genetic merit for fertility (FertBV). Genotypes of a previously identified SNP (rs109711583) in HSD17B12 were determined, with 116 animals genotyped as AA, 215 genotyped as AG, and 153 genotyped as GG. Plasma concentrations of prostaglandin E 2 and the PGF 2α metabolite PGFM were determined at 3 time points (12 mo of age, 4 d postpartum, and 5 wk postpartum during first lactation) in a selection of animals with AA and GG genotypes from both the POS and NEG FertBV groups (n = 33-40 in each genotype for each FertBV group). Binary reproductive traits (yes or no) examined included submission for artificial breeding in the first 3 or 6 wk of the seasonal breeding period; conception to first service; conception during the first 6 wk of the breeding period; and pregnant at the end of the breeding period. Uterine health at 6 wk after calving was examined by evaluating the percentage of polymorphonuclear leukocytes following uterine cytology and by scoring vaginal discharge based on the presence of purulent material. The 3-wk submission rate was increased in animals that carried the G allele of the missense SNP in HSD17B12, but no differences were present among genotypes for 6-wk submission rate. The trait was additive, with each increase of the G allele increasing the 3-wk submission rate by 6 to 7%. We did not observe any consistent associations between SNP alleles and circulating PGE 2 concentrations; however, a complex 3-way interaction among time, fertility group, and SNP allele was present for PGFM concentrations. Plasma concentrations of PGE 2 were increased approximately 40% at 5 wk postpartum in animals that were submitted for breeding within 3 or 6 wk of the start of the breeding season, and in those that conceived during the first 6 wk of breeding, compared with those that did not. Plasma concentrations of PGFM were decreased approximately 20% in those animals that conceived to their first service and tended to be decreased in animals that were pregnant at the end of the breeding period, compared with those that were not. In summary, associations were observed between the SNP in HSD17B12 and submission rate by d 21 of the breeding season, as well as between circulating prostaglandin concentrations and fertility traits, but the SNP was not consistently linked to changes in prostaglandin concentrations. Thus, the association between submission rate by d 21 of the breeding season and the SNP in HSD17B12 were unlikely driven by changes in prostaglandins.

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“…HSD17B12 is a member of the 17β-hydroxysteroid dehydrogenases, a class of enzymes that catalyze the interconversion of active and inactive steroid hormones [11]. HSD17B12 is widely expressed in animal kidneys, livers, and ovaries [12]. In addition, HSD17B12 has many important biological functions, including fatty acid metabolism, sex hormone production, and cell cycle regulation [12,13].…”

Section: Introductionmentioning

confidence: 99%

miR-136 Regulates the Proliferation and Adipogenic Differentiation of Adipose-Derived Stromal Vascular Fractions by Targeting HSD17B12

Liu,

Che,

Cai

et al. 2023

IJMS

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Fat deposition involves the continuous differentiation of adipocytes and lipid accumulation. Studies have shown that microRNA miR-136 and 17β-hydroxysteroid dehydrogenase type 12 (HSD17B12) play important roles in lipid accumulation. However, the regulatory mechanism through which miR-136 targets HSD17B12 during ovine adipogenesis remains unclear. This study aimed to elucidate the role of miR-136 and HSD17B12 in adipogenesis and their relationship in ovine adipose-derived stromal vascular fractions (SVFs). The target relationship between miR-136 and HSD17B12 was predicted and confirmed using bioinformatics and a dual-luciferase reporter assay. The results showed that miR-136 promoted proliferation and inhibited adipogenic differentiation of ovine SVFs. We also found that HSD17B12 inhibited proliferation and promoted adipogenic differentiation of ovine SVFs. Collectively, our results indicate that miR-136 facilitates proliferation and attenuates adipogenic differentiation of ovine SVFs by targeting HSD17B12. These findings provide a theoretical foundation for further elucidation of the regulatory mechanisms of lipid deposition in sheep.

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Functional genetic variant of HSD17B12 in the fatty acid biosynthesis pathway predicts the outcome of colorectal cancer

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 6 publications

References 54 publications

Emerging roles of polyunsaturated fatty acid synthesis pathway in colorectal cancer

Emerging roles of polyunsaturated fatty acid synthesis pathway in colorectal cancer

Relationships between prostaglandin concentrations, a single nucleotide polymorphism in HSD17B12, and reproductive performance in dairy cows

miR-136 Regulates the Proliferation and Adipogenic Differentiation of Adipose-Derived Stromal Vascular Fractions by Targeting HSD17B12

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