Long Noncoding RNA Regulator Of Reprogramming Research Articles

Linc-ROR Modulates the Endothelial-Mesenchymal Transition of Endothelial Progenitor Cells through the miR-145/Smad3 Signaling Pathway

The endothelial-mesenchymal transition (EndMT) of endothelial progenitor cells (EPCs) plays a notable role in pathological vascular remodeling. Emerging evidence indicated that long non-coding RNA-regulator of reprogramming (linc-ROR) can promote epithelial-mesenchymal transition (EMT) in a variety of cancer cells. Nevertheless, the function of linc-ROR in EPC EndMT has not been well elucidated. The present study investigated the effect and possible mechanisms of function of linc-ROR on the EndMT of EPCs. A linc-ROR overexpression lentiviral vector (LV linc-ROR) or a linc-ROR short hairpin RNA lentiviral vector (LV-shlinc-ROR) was used to up or downregulate linc-ROR expression in EPCs isolated from human umbilical cord blood. Functional experiments demonstrated that LV-linc-ROR promoted the proliferation and migration of EPCs, but inhibited EPC angiogenesis in vitro. In the meantime, reverse transcription-quantitative PCR and western blotting results showed that the expression of the endothelial cell markers vascular endothelial-cadherin and CD31 was decreased, while the expression of the mesenchymal cell markers α-smooth muscle actin and SM22α was increased at both mRNA and protein levels in LV-linc-ROR-treated EPCs, indicating that linc-ROR induced EPC EndMT. Mechanistically, the dual-luciferase reporter assay demonstrated that microRNA (miR/miRNA)-145 was a direct target of linc-ROR, and miR-145 binds to the 3’-untranslated region of Smad3. Moreover, LV-shlinc-ROR increased the expression of miR-145, but decreased the expression of Smad3. In conclusion, linc-ROR promotes EPC EndMT, which may be associated with the miR-145/Smad3 signaling pathway.

Expression and biological function of long non-coding RNA-regulator of reprogramming in gastric cancers

Objective To explore the expression of regulator of reprogramming (ROR) in human gastric cancer tissues and investigate the effects of ROR on biological behaviors in vitro. Methods Real-time quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) was used to detect the expression of ROR in 50 gastric cancer tissues and its paired normal tissues. To further explore its biological function, over-expression approach was used to up ROR expression. Normal control group (NC), plasmid control group (LV5-NC) and over-expression group (LV5-ROR)were transfected to in MGC-803, SGC-7901, and the transfection efficiency was evaluated by RT-qPCR. Cell counting kit-8 (CCK-8), transwell migration and invasion assays were performed to detect the biological effects of ROR in gastric cancer cells after transfection. Results The level of ROR was significantly down-regulated in gastric cancer compared with paired normal tissues samples (P 0.05). Transwell migration assay showed that the number of cells passing the membrance in LV5-ROR (336.33±34.93, 201.67±45.35) were decreased significantly than LV5-NC(841.67±38.19, 605.25±45.00)and NC 790.58±35.68, 620.59±49.00)(P<0.01). As is also in invasion assay, we further discovered the number of cells passing the membrance in LV5-ROR (253.33±41.63, 290.56±35.36) were lower than LV5-NC (757.67±52.73, 680.56±32.93) and NC (790.35±51.73, 780.35±32.85) (P<0.01). Conclusion Our results suggested that ROR was significantly down-regulated in gastric cancer tissues. These studies indicated over-expression of ROR in gastric cancer cells could suppressed invasion and migration, while had little effect on cell proliferation. ROR could prevent carcinogenesis and progression by inhibiting migration and invasion. Key words: Gastric cancer; Long non-coding RNA; Regulator of reprogramming

Long noncoding RNA-regulator of reprogramming alleviates hypoxia-induced cerebral injury in mice model and human via modulating apoptosis complexes.

Ischemic stroke causes cerebral hypoxia, while long non-coding RNA regulator of reprogramming is associated with hypoxia. To find a new intervention target to protect hypoxic cerebral tissue and a potential biomarker from reflecting the severity of hypoxia after ischemic stroke, our research explored the expression pattern and function of the regulator of reprogramming in cerebral hypoxia-induced injury. The expression pattern and the function of the regulator of reprogramming were explored in mice with middle cerebral artery occlusion, and human brain microvascular endothelial cells underwent oxygen-glucose deprivation treatment. A case-control study, including 223 ischemic stroke patients and 155 controls were also conducted to investigate its correlation with ischemic stroke clinical characteristics. Results showed that the regulator of reprogramming increased significantly in middle cerebral artery occlusion in mice (P < 0.05), and its level remained stable within 2 to 48 h after the implement of middle cerebral artery occlusion. Oxygen-glucose deprivation up-regulated the expression of regulator of reprogramming, and regulator of reprogramming promoted ASK-1/STRAP/14-3-3 complex formation to inhibit the activation of TNF-α/ASK-1-mediated apoptosis of human brain microvascular endothelial cells, while small interfering ribonucleic acid (RNA) targeting regulator of reprogramming amplified these effects. Regulator of reprogramming increased and maintained stable within 3 to 48 h of ischemic stroke onset in patients, and was negatively associated with the National Institutes of Health Stroke Scale (NIHSS) (r = -0.708, P < 0.001), high sensitivity C-reactive protein (Hs-CRP) (r = -0.683, P < 0.001) level, infarct volume (r = -0.579, P < 0.001), and modified Rankin scale (mRS) (r = -0.728, P < 0.001). These results indicate that the regulator of reprogramming can alleviate cerebral hypoxia-induced injury by suppressing TNFα-induced apoptosis of vascular endothelial cells.