MALAT1 expression in granulosa cells in PCOS patients with different phenotypes

Abstract

Polycystic ovary syndrome (PCOS) is one of the most common reproductive endocrine metabolic disorders. The lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) reportedly can regulate the reproductive system. Despite studies, the alteration of MALAT1 expression in granulosa cells (GCs) from PCOS patients was inconsistent. To evaluate MALAT1 expression in GCs in different PCOS subgroups and its association with PCOS phenotypes, we collected GCs from 110 PCOS cases and 71 controls, and examined MALAT1 expression by quantitative PCR. The results showed MALAT1 expression was upregulated in PCOS cases, especially in insulin resistant (IR) PCOS subgroup, obese PCOS subgroup and non-hyperandrogenic (NHA) PCOS subgroup. MALAT1 expression was positively correlated with BMI and several metabolic parameters in controls. Interestingly, MALAT1 expression was notably associated with some critical endocrine indexes for PCOS, including E2, FSH, LH and LH/FSH ratio. In different PCOS subgroups, we found significant positive correlations with LH/FSH ratio in IR-PCOS and PCOS with normal weight, and with serum T and LH level in NHA-PCOS subgroup. Integrated analysis with lncRNA target databases and PCOS-related databases revealed MALAT1 could participate in PCOS by influencing immune response and lipids metabolism in GCs. In conclusion, MALAT1 was differently expressed in GCs in PCOS, especially in IR, obese and NHA PCOS subgroups. MALAT1 was likely involved in metabolism and immune response in GCs in PCOS. However, more studies are necessary to establish this concept.

Keywords: Granulosa cells; Long noncoding RNA; MALAT1; Metabolism; Polycystic ovary syndrome.

Figure 1

MALAT1 expression was increased in GCs from PCOS, especially IR, NHA-PCOS and Obese subgroups. Data were normalized by Actin. (A) The relative expression of MALAT1 in PCOS cases (n = 110) and control women (n = 71). (B) The normalized expression of MALAT1 in IR-PCOS cases (n = 72), NIR-PCOS cases (n = 38) and control women (n = 71). (C) The normalized expression of MALAT1 in HA-PCOS cases (n = 31), NHA-PCOS cases (n = 79) and control women (n = 71). (D) The normalized expression of MALAT1 in PCOS cases with normal weight (n = 61), obese PCOS cases (n = 49), control women with normal weight (n = 62) and obese control women (n = 9).

Figure 2

MALAT1 expression was correlated with some clinical characteristics in controls and PCOS cases. (A–H) The relationships of MALAT1 expression and BMI, FPG, HOMA-IR, TG, E2, FSH, LH and LH/FSH ratio in control group and PCOS group. Statistical analysis of the data was performed using Spearman’s test. The blue dots represented control group and the red dots represented PCOS group.

Figure 3

MALAT1 expression was correlated with LH/FSH ratio in different PCOS subgroups. (A) The relationship of MALAT1 expression and LH/FSH ratio in controls, NIR-PCOS and IR-PCOS cases. (B) The relationship of MALAT1 expression and LH/FSH ratio in controls, obese controls, PCOS and obese PCOS cases. Statistical analysis of the data was performed using Spearman’s test.

Figure 4

MALAT1 expression was correlated with some clinical characteristics in controls, NHA-PCOS and HA-PCOS cases. (A) The relationship of MALAT1 expression and serum LH level in controls, NHA-PCOS and HA-PCOS cases. (B) The relationship of MALAT1 expression and serum TT level in controls, obese controls, PCOS and obese PCOS cases. Statistical analysis of the data was performed using Spearman’s test.

Figure 5

Regulation network of MALAT1 was generated by integrated analysis with public database. (A) Overlapped genes of MALAT1 target genes in LncRNA2Target and PCOS-related genes in OKdb. (B) Overlapped genes of MALAT1 target genes in RNA binding protein term in LncSEA and PCOS-related genes in OKdb, and these genes enrichment according to Reactome gene set. (C) Overlapped miRNAs of MALAT1 target miRNAs in microRNA term in LncSEA and PCOS-related miRNAs in PCOSKB.

Figure 6

Graphical summary.