CONTEXT: In adipose tissue (AT) micro-RNA-93 (miR-93) is significantly overexpressed in polycystic ovary syndrome (PCOS) women and non-PCOS women with insulin resistance (IR). Overexpressed miR-93 directly inhibits glucose transporter isoform 4, impairing both glucose metabolism and insulin sensitivity. The mechanisms behind increased miR-93 expression are unclear. OBJECTIVE: Our objective was to determine whether miR-93 expression is concordant with its host gene, MCM7, which contains the miR-25/93/106b gene cluster. PATIENTS: AT was excised from 16 women with PCOS (eight with and eight without IR) and 15 non-PCOS (nine with and six without IR). MAIN OUTCOME MEASURES: Expression of MCM7 and miR-25/93/106b was measured in AT and 3T3-L1 cells. RESULTS: MCM7 expression was lower in both non-PCOS/IR and PCOS women and tended to be lowest in women with PCOS and IR. Overall, the expression of MCM7 in human AT was negatively associated with miR-93 expression and with increased subject IR. Additionally, miR-25 and miR-106b expression is uncoupled from the MCM7 host gene and are positively correlated with IR, although no PCOS-specific difference was observed. MCM7 expression appears to be negatively correlated with increasing fasting glucose. In 3T3-L1 adipocytes, increasing glucose had no effect on miR-93 or miR-25, although it reduced MCM7 and increased miR-106b expression in a dose-dependent fashion. In turn, in 3T3-L1 adipocytes, increasing insulin had no effect on either MCM7 or miR-25/93/106b expression. CONCLUSIONS: Our data suggest that the expression of MCM7 and miR-93/25 is PCOS and IR related, whereas that of miR-106b is related to IR only. In 3T3-L1 adipocytes, neither hyperglycemia nor hyperinsulinemia altered the expression of miR-93 or miR-25, although increasing glucose levels down-regulated MCM7 and paradoxically increased that of miR-106b expression. The expression of the miR-25/93/106b family may be regulated through mechanisms distinct from its host gene, MCM7. Finally, our studies suggest potential epigenetic mechanisms for both IR and PCOS.
CONTEXT: In adipose tissue (AT) micro-RNA-93 (miR-93) is significantly overexpressed in polycystic ovary syndrome (PCOS) women and non-PCOSwomen with insulin resistance (IR). Overexpressed miR-93 directly inhibits glucose transporter isoform 4, impairing both glucose metabolism and insulin sensitivity. The mechanisms behind increased miR-93 expression are unclear. OBJECTIVE: Our objective was to determine whether miR-93 expression is concordant with its host gene, MCM7, which contains the miR-25/93/106b gene cluster. PATIENTS: AT was excised from 16 women with PCOS (eight with and eight without IR) and 15 non-PCOS (nine with and six without IR). MAIN OUTCOME MEASURES: Expression of MCM7 and miR-25/93/106b was measured in AT and 3T3-L1 cells. RESULTS:MCM7 expression was lower in both non-PCOS/IR and PCOSwomen and tended to be lowest in women with PCOS and IR. Overall, the expression of MCM7 in human AT was negatively associated with miR-93 expression and with increased subject IR. Additionally, miR-25 and miR-106b expression is uncoupled from the MCM7 host gene and are positively correlated with IR, although no PCOS-specific difference was observed. MCM7 expression appears to be negatively correlated with increasing fasting glucose. In 3T3-L1 adipocytes, increasing glucose had no effect on miR-93 or miR-25, although it reduced MCM7 and increased miR-106b expression in a dose-dependent fashion. In turn, in 3T3-L1 adipocytes, increasing insulin had no effect on either MCM7 or miR-25/93/106b expression. CONCLUSIONS: Our data suggest that the expression of MCM7 and miR-93/25 is PCOS and IR related, whereas that of miR-106b is related to IR only. In 3T3-L1 adipocytes, neither hyperglycemia nor hyperinsulinemia altered the expression of miR-93 or miR-25, although increasing glucose levels down-regulated MCM7 and paradoxically increased that of miR-106b expression. The expression of the miR-25/93/106b family may be regulated through mechanisms distinct from its host gene, MCM7. Finally, our studies suggest potential epigenetic mechanisms for both IR and PCOS.
Authors: Jan M McAllister; Angela X Han; Bhavi P Modi; Maria E Teves; Grace R Mavodza; Zachary L Anderson; Tsaiwei Shen; Lane K Christenson; Kellie J Archer; Jerome F Strauss Journal: Endocrinology Date: 2019-08-01 Impact factor: 4.736
Authors: Anja E Sørensen; Pernille B Udesen; Grzegorz Maciag; Julian Geiger; Negar Saliani; Andrzej S Januszewski; Guozhi Jiang; Ronald C Ma; Anandwardhan A Hardikar; Marie Louise M Wissing; Anne Lis M Englund; Louise T Dalgaard Journal: Front Med (Lausanne) Date: 2019-11-01
Authors: Justyna Strycharz; Ewa Świderska; Adam Wróblewski; Marta Podolska; Piotr Czarny; Janusz Szemraj; Aneta Balcerczyk; Józef Drzewoski; Jacek Kasznicki; Agnieszka Śliwińska Journal: Nutrients Date: 2018-11-15 Impact factor: 5.717
Authors: Alexandra E Butler; Vimal Ramachandran; Thozhukat Sathyapalan; Rhiannon David; Nigel J Gooderham; Manasi Benurwar; Soha R Dargham; Shahina Hayat; S Hani Najafi-Shoushtari; Stephen L Atkin Journal: Front Endocrinol (Lausanne) Date: 2020-04-28 Impact factor: 5.555