The Regulatory Network of CREB3L1 and Its Roles in Physiological and Pathological Conditions.

CREB3 subfamily belongs to the bZIP transcription factor family and comprises five members. Normally they are located on the endoplasmic reticulum (ER) membranes and proteolytically activated through RIP (regulated intramembrane proteolysis) on Golgi apparatus to liberate the N-terminus to serve as transcription factors. CREB3L1 acting as one of them transcriptionally regulates the expressions of target genes and exhibits distinct functions from the other members of CREB3 family in eukaryotes. Physiologically, CREB3L1 involves in the regulation of bone morphogenesis, neurogenesis, neuroendocrine, secretory cell differentiation, and angiogenesis. Pathologically, CREB3L1 implicates in the modulation of osteogenesis imperfecta, low grade fibro myxoid sarcoma (LGFMS), sclerosing epithelioid fibrosarcoma (SEF), glioma, breast cancer, thyroid cancer, and tissue fibrosis. This review summarizes the upstream and downstream regulatory network of CREB3L1 and thoroughly presents our current understanding of CREB3L1 research progress in both physiological and pathological conditions with special focus on the novel findings of CREB3L1 in cancers.

LINC00665 rescues bupivacaine induced neurotoxicity in human neural cell of SH-SY5Y through has-miR-34a-5p.

BACKGROUND: Excessive application of local anesthetics, bupivacaine (BUP) may induce neurotoxicity and lead to neurologic dysfunctions in human brains. Yet, the exact molecular mechanisms underlying BUP-induced neurotoxicity was not fully understood. In this study, we utilized an in vitro SH-SY5Y cell culture model to explore the functional mechanism of long intergenic non-protein coding RNA 665 (LINC00665) in regulating BUP-induced neurotoxicity. METHODS: SH-SY5Y cells were induced with BUP in vitro, and their viability and apoptosis were monitored. BUP-induced LINC00665 expression was also monitored, by qRT-PCR. LINC00665 was then overexpressed in SH-SY5Y cells, and its effects on BUP-induced neurotoxicity were investigated. The downstream target transcript of LINC00665, human mature microRNA-34a-5p (hsa-miR-34a-5p) was investigated in BUP-induced SH-SY5Y cells. Co-regulation of LINC00665 / hsa-miR-132-3p epigenetic axis was further examined on BUP-induced apoptosis in SH-SY5Y cells. RESULTS: BUP reduced cell viability, induced apoptosis and downregulated LINC00665 in SH-SY5Y cells. LINC00665 overexpression rescued BUP-induced neurotoxicity in SH-SY5Y cells. Hsa-miR-34a-5p expression was directly correlated with BUP treatment and LINC00665 overexpression in SH-SY5Y cells. Upregulating hsa-miR-34a-5p reversed the rescuing effects of LINC00665 on BUP-induced SH-SY5Y apoptosis. CONCLUSIONS: BUP-induced neurotoxicity in human neural cells may be regulated by the epigenetic axis of LINC00665 / hsa-miR-34a-5p.