Long non-coding RNA H19 regulates proliferation of ovarian granulosa cells via STAT3 in polycystic ovarian syndrome

Abstract

Introduction: Studies have shown that long non-coding RNAs (lncRNA) are aberrantly expressed in polycystic ovarian syndrome (PCOS) ovaries and may have a role in PCOS development. In this study, the role and therapeutic implications of lncRNA H19 were investigated in PCOS ovaries and granulosa cells. Material and methods: qRT-PCR was used for expression analysis. Cell Counting Kit 8 (CCK-8) assay was used for cell viability and acridine orange/ ethidium bromide (AO/EB) and Annexin V/propidium iodide staining was used to detect apoptosis. All transfections were carried out with Lipofectamine 2000 reagent. Western blot analysis was used for protein expression analysis. Results: The expression of lncRNA H19 was remarkably upregulated in the PCOS ovarian tissues as well as the granulosa cells. Suppression of lncRNA H19 expression caused the inhibition of KGN granulosa cell proliferation due to the triggering of apoptosis. Bioinformatic analysis revealed the presence of the GAS binding site for STAT3 in the promoter of lncRNA H19. Silencing of STAT3 suppressed the expression of lncRNA H19 in KGN cells and also halted their growth by triggering apoptosis. Co-transfect experiments revealed that STAT3 and lncRNA H19 silencing cause inhibition of KGN growth synergistically. Conclusions: lncRNA H19 regulates the growth of ovarian granulosa cells and might prove to be a therapeutic target for management of PCOS.

Identification of biomarkers and pathways for focal segmental glomerulosclerosis using next generation sequencing data and bioinformatics analysis

“…Altered expression and activity of STAT3 [590], STAT1 [591] and GATA3 [592] have been demonstrated in diabetes mellitus. As previously reported, EZH2 [593] is altered expressed in polycystic ovarian syndrome. STAT3 [594], STAT1 [594] and GATA3 [595] were a diagnostic markers of multiple sclerosis and could be used as therapeutic targets.…”

LncRNA‐412.25 activates the LIF/STAT3 signaling pathway in ovarian granulosa cells of Hu sheep by sponging miR‐346

“…56 STATs are a family of transcription factors that mediate cytokine signaling, such as LIF, and stimulate cell proliferation. 45,57 Moreover, LIF/STAT3 pathway is reported to be involved in follicular development, 48 differentiation, 58 and cell self-renewal. 59 In the present study, we found that Hu sheep GCs were able to respond to LIF by monitoring STAT3 activation following the overexpression of LIF.…”

“…55 Additionally, increasing evidence has indicated that lncRNA or miRNA activate the LIF/STAT3 pathway to regulate cellular state and function. 57,[60][61][62] The most significant result of this study indicated that lncRNA-412.25 activated the LIF/STAT3 pathway-mediated GCs state by interacting with miR-346 in Hu sheep.…”

Mitochondrial Dysfunction and Chronic Inflammation in Polycystic Ovary Syndrome

“…LncRNA H19, the other known cancer progression biomarker [ 185 ], is also upregulated in PCOS patients and has been shown to interact with STAT3, synergistically regulating ovarian cells viability [ 186 ]. LncRNA SRA (steroid receptor RNA activator), known to be linked with several diseases and types of cancer [ 187 ], is upregulated in PCOS patients and linked to proinflammatory cytokine production (TNF-α, IL-1β and IL-6) and higher IR levels [ 188 ].…”