Long noncoding RNA OR3A4 promotes the migration and invasion of melanoma through the PI3K/AKT signaling pathway.

The article "Long noncoding RNA OR3A4 promotes the migration and invasion of melanoma through the PI3K/AKT signaling pathway, by J. Wu, M.-Y. Zhou, X.-P. Yu, Y. Wu, P.-L. Xie, published in Eur Rev Med Pharmacol Sci 2019; 23 (16): 6991-6996-DOI: 10.26355/eurrev_201908_18739-PMID: 31486499" has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18739.

Long noncoding RNA OR3A4 promotes the migration and invasion of melanoma through the PI3K/AKT signaling pathway.

OBJECTIVE: Recent studies have revealed the crucial role of long non-coding RNAs (lncRNAs) in tumor progression. This study aims to identify the biological function of lncRNA OR3A4 in the progression of melanoma. PATIENTS AND METHODS: OR3A4 expression in melanoma cells and tissue samples was detected by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR). The regulatory effects of OR3A4 on melanoma cells were identified by performing transwell assay and wound healing assay in vitro. The underlying mechanism of OR3A4 in mediating the progression of melanoma was explored by RT-qPCR and Western blot. RESULTS: OR3A4 expression was remarkably upregulated in melanoma tissues compared with normal tissues. Moreover, migration and invasion of melanoma cells were inhibited after knockdown of OR3A4 in vitro, which were promoted after overexpression of OR3A4. Furthermore, the targeted proteins in phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway were downregulated after knockdown of OR3A4 in vitro, which were upregulated by overexpressed OR3A4. CONCLUSIONS: OR3A4 could promote the invasion and migration of melanoma cells by inducing the PI3K/AKT signaling pathway, which may offer a new therapeutic intervention for melanoma patients.

Omentin-1 exerts bone-sparing effect in ovariectomized mice.

UNLABELLED: Omentin-1 inhibited osteoblast differentiation in vitro. In co-culture systems of osteoblasts and osteoclast precursors, omentin-1 reduced osteoclast formation by stimulating osteoprotegerin (OPG) and inhibiting receptor activator for nuclear factor κB ligand (RANKL) production in osteoblasts. In vivo, adenovirus-mediated overexpression of omentin-1 suppressed bone turnover and restored bone mineral density (BMD) and bone strength in ovariectomized mice. INTRODUCTION: Omentin-1 (also intelectin-1) is a recently identified visceral adipose tissue-derived cytokine that is highly abundant in plasma. This study was undertaken to investigate the effects of omentin-1 on bone metabolism. METHODS: Osteoblast differentiation was assessed by measuring alkaline phosphatase activity, osteocalcin production and matrix mineralization. OPG and RANKL protein expression and secretion in osteoblasts were detected by Western blot and ELISA, respectively. The effect of recombinant omentin-1 on osteoclast formation was examined in co-culture systems of osteoblasts and osteoclast precursors. The effects of intravenous administration of adenoviral-delivered omentin-1 on bone mass, bone strength, and bone turnover were also examined in ovariectomized mice. RESULTS: In vitro, omentin-1 inhibited osteoblast differentiation, while it had no direct effect on osteoclast differentiation; it also reduced osteoclast formation in the co-culture systems through stimulating OPG and inhibiting RANKL production in osteoblasts. In vivo, adenovirus-mediated overexpression of omentin-1 partially restored BMD and bone strength in ovariectomized mice, accompanied by decreased levels of plasma osteocalcin and tartrate-resistant acid phosphatase-5b and lower serum RANKL/OPG ratios. CONCLUSION: The present study suggests that omentin-1 ameliorates bone loss induced by estrogen deficiency via downregulating the RANKL/OPG ratio.

Expression of receptor for advanced glycosylation end products (AGEP) and inhibition of AGEP-induced cytosolic calcium elevation by diltiazem in cultured rat aortic smooth muscle cells.

AIM: To study whether there is a high affinity receptor for advanced glycosylation end product (AGEP) on thoracic aorta smooth muscle cells (ASMC) and to test effect of diltiazem on elevation of cytosolic free calcium induced by AGEP. METHODS: Interactions of AGEP-bovine serum albumin (BSA) with ASMC were studied with radioligand binding assay and cytosolic free calcium ([Ca2+]i) was examined in cultured ASMC with Fura 2-AM. RESULTS: AGEP-BSA was specifically bound to cells at 4 degrees C and was taken up and degraded at 37 degrees C. These processes were concentration-dependent and saturable. Scatchard analysis indicated that the receptor was with dissociation constant of 65.3 +/- 1.5 nmol.L-1 and its maximal binding capacity of 1.57 +/- 0.04 nmol/g cell protein. Early glycated low density lipoprotein (LDL) was not recognized by this receptor. AGEP-BSA elevated cytosolic free calcium in a concentration-dependent manner. Pretreatment with diltiazem inhibited AGEP-BSA-induced elevation in concentration- and time-dependent manners. CONCLUSION: There was a high affinity receptor for AGEP on ASMC, which mediated internalization and degradation of AGEP. Pretreatment with diltiazem inhibited the AGEP-induced elevation of cytosolic free calcium.

Interactions between ANP and ANG II in regulating blood pressure and sympathetic outflow.

In anesthetized rats with sinoaortic denervation, intracerebroventricular (icv) injection of atrial natriuretic peptide (ANP) resulted in decreased mean arterial blood pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) (depressor effects), whereas icv angiotensin II (ANG II) produced increases in these variables (pressor effects). The depressor effects of ANP were slower in onset and longer in duration than the pressor effects of ANG II. Intracerebroventricular injection of the ANG II-receptor blocker sarthran or the ANG II-synthesis inhibitor captopril resulted in a significant reduction in MAP; HR and RSNA were not affected. Both sarthran and captopril abolished the depressor responses to icv ANP. In contrast, injection of an anti-rat ANP antibody, which blocked the depressor effects of icv ANP, did not by itself modify MAP, HR, or RSNA, nor did the antibody affect the pressor responses to icv ANG II. These data suggest that, in this animal model, the depressor effects of icv ANP are mediated by the inhibition of brain ANG II-dependent neural activity. These results also demonstrate that, in this preparation, the endogenous ANG II system actively contributes to the maintenance of basal MAP, whereas the central ANP system, at least in regions accessible to the antirat ANP antibody, plays little role in this maintenance.

Rapid baroreceptor resetting in chronic hypertension. Implications for normalization of arterial pressure.

The purpose of this study was to examine the ability of baroreceptors of renal hypertensive rabbits to reset rapidly during acute changes in arterial pressure. The carotid sinus (CS) was vascularly isolated and baroreceptor activity was recorded during slow ramp increases in CS pressure in hypertensive (one-kidney, one wrap; 127 +/- 3 mm Hg) and normotensive (one-kidney, no wrap; 85 +/- 3 mm Hg) rabbits anesthetized with chloralose. Control measurements were made after holding pressure for 10-15 minutes at the level of arterial pressure recorded before each experiment. Baroreceptor threshold pressure (Pth) was higher in hypertensives (78 +/- 4 mm Hg) compared with normotensives (55 +/- 3 mm Hg, p less than 0.05), and nerve activity was less in hypertensives over a wide range of pressure. CS distensibility (sonomicrometers) was not significantly different in the two groups. After increasing holding pressure from control by 30 and 60 mm Hg for 10-15 minutes, the extent of baroreceptor resetting (delta Pth/delta holding pressure x 100%) in normotensives was 39 +/- 6% and 33 +/- 2%, respectively, but only 14 +/- 5% and 9 +/- 3% in hypertensives (p less than 0.05). After decreasing holding pressure by 30 and 60 mm Hg, resetting was similar in normotensives (32 +/- 6% and 28 +/- 3%) and hypertensives (34 +/- 3% and 30 +/- 4%). In hypertensive rabbits, acute (10-15 minutes) exposure of baroreceptors to normotension (71 +/- 4 mm Hg) decreased Pth to 62 +/- 4 mm Hg and increased nerve activity to levels not significantly different from those of normotensive animals without altering CS distensibility.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism of decreased baroreceptor activity in chronic hypertensive rabbits. Role of endogenous prostanoids.

We examined the contribution of endogenous prostanoids to baroreceptor activation in chronic renal hypertension. Baroreceptor activity was recorded from the vascularly isolated carotid sinus during slow ramp increases in pressure in rabbits anesthetized with pentothal and chloralose. Mean arterial pressure averaged 133 +/- 4 mmHg in hypertensive rabbits (one kidney, one wrap, n = 12) and 85 +/- 3 mmHg in normotensive rabbits (one kidney, no wrap, n = 13). Baroreceptor activity was decreased significantly (P less than 0.05) in the hypertensive compared with the normotensive rabbits. The decreased baroreceptor activity could not be explained by decreased distensibility of the carotid sinus (sonomicrometers). Inhibition of the endogenous formation of prostanoids with intrasinus administration of indomethacin (50 microM) decreased baroreceptor activity in normotensive (P less than 0.05) but not in hypertensive rabbits over a wide range of pressures. At a pressure of 120 mmHg, activity declined from 61 +/- 14 spikes/s before indomethacin to 47 +/- 12 spikes/s with indomethacin, i.e., a drop of 24 +/- 4%. In contrast, corresponding values in hypertensive rabbits averaged 41 +/- 13 and 40 +/- 12 spikes/s (-1 +/- 2%). Intrasinus prostacyclin, on the other hand, increased activity in both groups: at 120 mmHg activity increased from 62 +/- 9 to 92 +/- 15 spikes/s (51 +/- 17%) in normotensive rabbits and from 29+/- 7 to 47 +/- 14 spikes/s (68 +/- 23%) in hypertensive rabbits. Neither indomethacin nor prostacyclin (n = 5) influenced the pressure-diameter relation of the carotid sinus. The increase in prostacyclin (6-keto-PGF 1 alpha) formation by the sinus in response to its exposure to arachidonic acid (10 microM) was significant (P less than 0.05) in the normotensives (1,627 +/- 344%; n = 5) but not in the hypertensives (583 +/- 353%; n = 5). We conclude that the decreased baroreceptor activity in chronic hypertension may not be caused by decreased distensibility of the vascular wall of the sinus and that endogenous prostanoids that contribute to baroreceptor activation in normotensive rabbits fail to do so in hypertensive rabbits. This appears to be due to decreased formation of prostacyclin rather than decreased sensitivity of the baroreceptors to prostacyclin. The results suggest a new mechanism that contributes to chronic baroreceptor resetting in hypertension.