Long non-coding RNAs TUG1 and MEG3 in patients with type 2 diabetes and their association with endoplasmic reticulum stress markers

J Endocrinol Invest. 2023 Jul;46(7):1441-1448. doi: 10.1007/s40618-023-02007-5. Epub 2023 Jan 20.

Abstract

Background: Long non-coding RNAs (lncRNAs), including taurine upregulated gene 1 (TUG1), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), and maternally expressed 3 (MEG3) play a regulatory role in endoplasmic reticulum (ER) stress. The present study aimed to investigate the expression of these lncRNAs in patients with type 2 diabetes and their association with biochemical and ER stress parameters.

Materials and methods: Participants included 57 patients with diabetes and 32 healthy individuals. Real-time PCR was performed to assess MALAT1, TUG1, MEG3, ATF4, and CHOP gene expression in peripheral blood mononuclear cells. Plasma GRP78, advanced glycation end products (AGEs), and insulin were measured using enzyme-linked immunosorbent assay (ELISA), and insulin resistance (IR) was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR).

Results: The expression of TUG1, MEG3, ATF4, and CHOP genes was significantly increased in the patients with diabetes compared to healthy individuals. MALAT1 gene expression was also higher in patients group; although it did not reach significant levels. TUG1 and MEG3 expression revealed significant positive correlations with the indices of glycemic control, including FBS, HbA1c, HOMA-IR, and AGEs, as well as markers of ER stress. MALAT1 expression was also positively correlated with ATF4 and AGEs.

Conclusion: The expression levels of TUG1 and MEG3 lncRNAs were increased in patients with diabetes and were associated with glycemic control and components of ER stress. Thus, these lncRNAs might be considered appropriate markers to identify ER stress due to hyperglycemia.

Keywords: ATF4; CHOP; Endoplasmic reticulum stress; MALAT1; MEG3; TUG1; Type 2 diabetes (T2D).

MeSH terms

  • Diabetes Mellitus, Type 2*
  • Endoplasmic Reticulum Stress
  • Glycation End Products, Advanced
  • Humans
  • Insulin Resistance*
  • Leukocytes, Mononuclear / metabolism
  • RNA, Long Noncoding* / genetics

Substances

  • RNA, Long Noncoding
  • Glycation End Products, Advanced