Downregulation of HOTTIP regulates insulin secretion and cell cycle in islet β cells via inhibiting MEK/ERK pathway

OBJECTIVE: To investigate the effect of long non-coding RNA (IncRNA) HOTTIP on islet 13 cells and its underlying mechanism. MATERIALS AND METHODS: The expressions of HOTTIP in different organs of db/db mice and C57BL/6J mice were detected by quantitative Real-time polymerase chain reaction (qRT-PCR). Effects of HOTTIP on the proliferation, insulin secretion and apoptosis of islet beta cells transfected with lentivirus were detected by cell counting kit-8 (CCK-8) assay, enzyme-linked immunosorbent assay, (ELISA) and flow cytometry, respectively. We also assessed the protein expressions of key genes in MEK/ERK pathway by using Western blot. RESULTS: HOTTIP was upregulated in normal islet tissues of C57BL/6J mice but downregulated in islet tissues of diabetic mice. Inhibition of HOTTIP attenuated insulin secretion and reduced expressions of Pdx1 and MafA. Down regulation of HOTTIP also inhibited cell proliferation and reduced expressions of CyclinDI, CyclinD2, CyclinE1 and CyclinE2. Moreover, islet beta cells were arrested in GO/G1 phase after HOTTIP knockdown. Our data showed that the biological function of HOTTIP in regulating insulin secretion and cell cycle in islet beta cells might be related to the MEK/ERK pathway. CONCLUSIONS: Downregulation of HOTTIP inhibits insulin secretion and cell cycle in islet beta cells via MEK/ERK pathway.