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. 2022 Jan 6;26(3):654–670. doi: 10.1111/jcmm.17139

TABLE 2.

Summarizing the finding for lncRNAs regarding polycystic ovary syndrome

Team Main LncRNAs Notes and findings
Butler et al. 2019 82

AC005332.6 MALAT1

AC009404.1

MIR181A1HG

PSMG3‐AS1

  • No lncRNA correlated with anti‐mullerian hormone (AMH) levels, insulin resistance (HOMA‐IR) or the free androgen index (FAI).

  • LncRNAs differ between anovulatory PCOS and control women in the follicular phase of the menstrual cycle

Tan et al. 83 LncRNA SRA1
  • LncRNA SRA1 gene single‐nucleotide polymorphism correlated to polycystic ovary syndrome

Jiao et al. 84
  • LncRNA and mRNA profiles in follicular fluid from mature and immature ovarian follicles of healthy women and women with PCOS, construction of the mRNA/lncRNA network

  • Good example of systematic transcriptome‐wide analysis

Fawzy et al. 85 Circ‐LncRNAs: H19, GAS5
  • Also, associated with type 2 diabetes

Huang et al. 44 LncRNA‐PWRN2
  • Construction of a lncRNA‐PWRN2‐ ceRNA network suggests its potential roles in oocyte nuclear maturation in PCOS patients

Ma et al. 38

LINC00667, H19, AC073172.1

  • Construction of PCOS related lncRNA‐mRNA network

  • Three main PCOS related lncRNAs were involved in the NF‐kB signaling pathway, inflammatory, apoptotic and immune‐related processes

Huang et al. 37 Exosomal circLDLR
  • CircLDLR increased miR−1294 expression and inhibited CYP19A1 expression in recipient cells

  • Related to ovarian steroidogenesis, aldosterone synthesis and secretion, and Jak‐STAT signaling.

  • From follicular fluid

Bouckenheimer et al. 86 LncRNAs: NEAT1, XIST, TSIX, VIM‐AS1, MEG3 and H19
  • Differential lncRNA expression profiles in human oocytes and cumulus cells,

  • MII oocyte lncRNAs could be involved in chromatin remodeling, cell pluripotency and in driving early embryonic development.

Jiang et al. 87 LncRNA‐HOTAIR
  • Downregulated lncRNA‐HOTAIR alleviates PCOS by reducing expression of insulin‐like growth factor 1 via miRNA−130a, on ovarian tissues of rat

Zhen et al. 88 LncRNA NEAT1/miR−381/IGF1
  • Downregulated lncRNA NEAT1 upregulates microRNA−381 to induce proliferation

  • and repress apoptosis of ovarian granulosa cells in PCOS rat,

  • Through inhibiting IGF1 expression.

  • LncRNA NEAT1 acted as a competing endogenous RNA to adsorb miR−381, and IGF1 was verified to be a direct target gene of miR−381.

Wu et al. 89 Lnc‐OC1
  • Its downregulation associated with PCOS, in granulosa cells

Lin et al. 90 LncRNA GAS5
  • Downregulation of lncRNA‐GAS5 may contribute to insulin resistance in PCOS patients

  • From serum

Liu et al. 91 LncRNA‐Xist
  • Xist downregulation may be involved in PCOS and is correlated with adverse pregnant outcomes in PCOS

  • From serum

Wang et al. 92

lncRNA‐H19

  • high‐throughput lncRNA sequencing of follicular fluid exosomes in non‐PCOS infertility patients and PCOS infertility patients

  • In exosomes from follicular fluid

  • lncRNA‐H19 represented the largest node and was predicted to have the potential to interact with 15 target miRNAs

Zeng et al. 30

lncRNAs (KLF3‐AS1, WWC2‐AS, and MAPKAPK5‐AS1)

miRNAs(miR−382)

  • Construction of a drug molecule and RNA network

  • Based on co‐expression and ceRNA network analyses

Zhang et al. 93 lncRNA CD36–005
  • Identification of mRNAs related to endometrium function regulated by lncRNA CD36–005 in rat endometrial stromal cells

  • Providing a list of potential target mRNA genes of CD36–005 in endometrial stromal cells and laid a foundation for further studies on the molecular function and mechanism of CD36–005 in the endometrium helping to unfold the PCOS

Geng et al. 94 lncRNA‐MAP3K13‐7:1
  • Inhibits ovarian granulosa cells proliferation in PCOS via DNMT1 downregulation

  • In KGN cells

  • lnc‐MAP3K13‐7:1 overexpression resulted in cell cycle arrest in the G0/G1 phase, as well as the molecular inhibition and genetic silencing of DNMT1.

Yang et al. 95 LncRNA‐BANCR
  • Role in PCOS by promoting apoptosis in granulosa cells

  • From cells of IVF patients

Wang et al. 54 LncRNA‐GAS5
  • LncRNA‐GAS5 is upregulated in polycystic ovary syndrome and regulates cell apoptosis and the expression of IL−6 in granulosa cells

  • From blood plasma

Sun et al. 53 lncRNA‐H19
  • lncRNA H19 acts as a ceRNA to regulate the expression of CTGF by targeting miR−19b in PCOS

  • On KGN cell line

  • H19 could promote cell proliferation and decrease cell apoptosis

Chen et al. 96 LncRNA‐HCP5
  • LncRNA‐HCP5 promotes cell proliferation and inhibits apoptosis via miR−27a−3p/IGF−1 axis

  • On human granulosa‐like tumor cell line KGN

Guo et al. 97 LncRNA‐HOTAIRM1
  • LncRNA‐HOTAIRM1/miR−433‐5p/PIK3CD function as a ceRNA network to encourage the development of PCOS

Han et al. 98 LncRNA‐LET
  • LncRNA‐LET inhibits cell viability, migration and EMT while induces apoptosis by up‐regulation of TIMP2

  • On KGN cell line

Liu et al. 99 lncRNA PVT1
  • lncRNA‐PVT1/MicroRNA−17‐5p/PTEN axis regulates secretion of E2 and P4, proliferation, and apoptosis of ovarian granulosa cells

Butler et al. 2020 100

LINC01539, AC095350.1,

LINC00616

  • LncRNA Expression in Non‐obese PCOS and weight matched controls

  • Differed in serum

Qin et al. 101 LncRNA‐H19
  • LncRNA‐H19 is associated with PCOS in Chinese women

  • From peripheral blood leukocytes

Huang et al. 47 Lnc‐CCNL1‐3:1
  • lnc‐CCNL1‐3:1 promotes granulosa cell apoptosis and suppresses glucose uptake in PCOS

  • From human luteinized granulosa cells(hLGCs) derived from women

Zhao et al. 102 LINC−01572:28
  • LINC−01572:28 inhibits granulosa cell growth via a decrease in p27 in PCOS

Sang et al. 103 LncRNA‐NEAT1
  • LncRNA‐NEAT1 drives the development of PCOS via sponging multiple miRNAs

Youssef et al. 104 LncRNA steroid receptor activator (SRA)
  • LncRNA‐SRA has positive correlation with hirsutism, obesity, testosterone, and insulin resistance in PCOS patients.

  • LncRNA‐SRA may be a mediator in the pathogenesis of both metabolic and hormonal syndromes.

Li et al. 105 LncRNA‐TUG1
  • Molecular mechanisms for LncRNA‐TUG1 in PCOS

Che et al. 106 lnc‐ZSCAN2‐5:15
  • Promotes follicular fluid androgen excess in PCOS patients via aromatase inhibition.

  • In granulosa cells derived from PCOS and non‐PCOS women

Liu et al. 17 Lacking to provide p‐values for the greatly changed markers
  • Using human granulosa cells (GCs) and the KGN cell line.

Zhang et al. 36 LncRNA‐MALAT1
  • lncRNA‐MALAT1 is involved in the pathogenesis of PCOS through TGFβ signaling in granulosa cells

  • A nice biomolecule for possible future RNA therapy, repeated in literature

Wang et al. 107 LncRNA‐H19
  • Metformin and sitagliptin combination therapy is effective for PCOS with insulin resistance through upregulation of lncRNA‐H19. To summarize, co‐treatment induced H19 expression via suppressing the PI3K/AKT‐DNMT1 pathway.

Ma et al. 50

circRNA_0043533,

circRNA_0043532,

circRNA_0097636

  • Serum testosterone (T) level positively correlated with the expression of circRNA_0043533 and circRNA_0097636 in the PCOS group

  • Dysregulated circRNAs were possibly involved in cell cycle, oocyte meiosis, progesterone‐mediated oocyte maturation, the FOXO signaling pathway, phosphatidylinositol signaling and glycerophospholipid metabolism

Zhao et al. 108 LncRNA RP11151A6.4
  • RP11151A6.4 was identified as a hub lncRNA based on IRLMN and WGCNA and was highly expressed in ovarian granulosa cells, skeletal muscle, and subcutaneous and omental adipose tissues of patients with insulin resistance

  • Relationships with: insulin resistance, androgen excess, and adipose dysfunction in PCOS patients

Jin et al. 109 LncRNA‐NONHSAT102254
  • In ovarian granulosa cells from women with PCOS with or without hyperandrogenism

  • dysregulated lncRNA in PCOS have a regulatory role in mitochondrial function via interacting with transcription factors such as YY1 and SIX5.

Gao et al. 110 LINC00477
  • The LINC00477/miR−128 axis promotes the progression of PCOS, via regulating ovarian granulosa cell proliferation and apoptosis.

  • From serum of patients and model.

Li et al. 111 LncRNA‐SRA
  • Up‐regulation LncRNA‐SRA promotes cell growth, inhibits cell apoptosis, and induces secretion of estradiol and progesterone.

  • From ovarian granular cells of mice.

  • Elevated LncRNA stimulated cell growth, changed distribution of cell cycle phases with increase of Cyclins B, E, and D1, and inhibited cell apoptosis with increment of bcl2 and decrease of bax, cleaved‐caspase 3, and cleaved‐PARP.

Li et al. 112 lncRNA‐SRLR
  • Upregulation of the lncRNA‐SRLR regulates cell apoptosis and increases levels of interleukin−6 (IL−6).

  • Also, in renal cell carcinoma, the lncRNA‐SRLR upregulates IL−6.

Fu et al. 46 Expression profiles of mRNA and lncRNA
  • LncRNA–miRNA–mRNA network was constructed

  • On rat ovaries through deep sequencing

Zhao et al. 31 circ_0023942
  • circ_0023942 inhibits the proliferation of human ovarian granulosa cell