Paramagnetic Resonance of Cobalt(II) Trispyrazolylmethanes and Counterion Association

Numerous studies have reported that the long non-coding RNA (lncRNA) small nucleolar RNA host gene 6 (SNHG6; ENSG00000245910) participates in the development of malignant tumors. However, the underlying mechanism of SNHG6 in the development of melanoma remains unknown. Thus, the present study aimed to investigate the biological role of SNHG6 in the progression of melanoma. SNHG6 expression in melanoma tissues and cells was assessed using a bioinformatics approach and reverse transcription-quantitative PCR analysis. Cell viability was determined using the Cell Counting Kit-8 and colony formation assays. The correlation between microRNA (miR)-101-3p, SNHG6 and RAP2B expression levels was assessed using Pearson's correlation analysis. Bioinformatic analysis and luciferase reporter assay were utilized to confirm the interaction between miR-101-3p and SNHG6 or RAP2B. The Transwell assay was conducted to examine the migratory and invasive activities of melanoma cells. In the present study, SNHG6 expression was upregulated in melanoma tissues and cell lines, and SNHG6 silencing suppressed melanoma cell viability, migration and invasion. SNHG6 was directly bound to miR-101-3p, which interacted with RAP2B. In addition, miR-101-3p expression was negatively correlated with SNHG6 or RAP2B expression. miR-101-3p silencing partially abrogated the suppressive effect of SNHG6-knockdown on RAP2B expression. Moreover, the data demonstrated that RAP2B overexpression reversed the inhibitory effects on melanoma cell proliferation, migration and invasion induced by SNHG6 silencing. In conclusion, the present study identified that SNHG6 accelerated melanoma progression via regulating the miR-101-3p/RAP2B axis. Thus, the SNHG6/miR-101-3p/RAP2B signaling pathway may be a novel therapeutic target for melanoma.

show abstract

“…5D and E ). Collectively, the data demonstrated that SNHG6 may accelerate melanoma progression by increasing RAP2B expression ( 17 ).…”

Section: Resultsmentioning

confidence: 99%

Long non‑coding RNA SNHG6 promotes tumorigenesis in melanoma cells via the microRNA‑101‑3p/RAP2B axis

Zhou

Wang

et al. 2020

Oncol Lett

View full text Add to dashboard Cite

show abstract

“…These chemical shifts are consistent with previously-reported spectra of Tp-based Co(ii) complexes. 69,70 The spectrum of 4 is more complex; in addition to the four Tp Me2 -derived features, it displays a series of peaks arising from the CysOEt ligand (marked with the black dots in Fig. 2).…”

Section: Resultsmentioning

confidence: 99%

Spectroscopic and computational studies of reversible O₂ binding by a cobalt complex of relevance to cysteine dioxygenase

2017

View full text Add to dashboard Cite

The substitution of non-native metal ions into metalloenzyme active sites is a common strategy for gaining insights into enzymatic structure and function. For some nonheme iron dioxygenases, replacement of the Fe(ii) center with a redox-active, divalent transition metal (e.g., Mn, Co, Ni, Cu) gives rise to an enzyme with equal or greater activity than the wild-type enzyme. In this manuscript, we apply this metal-substitution approach to synthetic models of the enzyme cysteine dioxygenase (CDO). CDO is a nonheme iron dioxygenase that initiates the catabolism of l-cysteine by converting this amino acid to the corresponding sulfinic acid. Two mononuclear Co(ii) complexes (3 and 4) have been prepared with the general formula [Co(Tp)(CysOEt)] (R = Ph (3) or Me (4); Tp = hydrotris(pyrazol-1-yl)borate substituted with R-groups at the 3- and 5-positions, and CysOEt is the anion of l-cysteine ethyl ester). These Co(ii) complexes mimic the active-site structure of substrate-bound CDO and are analogous to functional iron-based CDO models previously reported in the literature. Characterization with X-ray crystallography and/or H NMR spectroscopy revealed that 3 and 4 possess five-coordinate structures featuring facially-coordinating Tp and S,N-bidentate CysOEt ligands. The electronic properties of these high-spin (S = 3/2) complexes were interrogated with UV-visible absorption and X-band electron paramagnetic resonance (EPR) spectroscopies. The air-stable nature of complex 3 replicates the inactivity of cobalt-substituted CDO. In contrast, complex 4 reversibly binds O at reduced temperatures to yield an orange chromophore (4-O). Spectroscopic (EPR, resonance Raman) and computational (density functional theory, DFT) analyses indicate that 4-O is a S = 1/2 species featuring a low-spin Co(iii) center bound to an end-on (η) superoxo ligand. DFT calculations were used to evaluate the energetics of key steps in the reaction mechanism. Collectively, these results have elucidated the role of electronic factors (e.g., spin-state, d-electron count, metal-ligand covalency) in facilitating O activation and S-dioxygenation in CDO and related models.

show abstract

“…By contrast, the closed-form expressions above allow us to limit the variable parameters to just the electron relaxation times. For example, our previous work on methyl-substituted derivatives of [Co(Tpm) 2 ]-[BF 4 ] 2 provided NMR-derived (and ENDOR-verified) measures of the contact coupling strengths (A iso ), 14 leaving only T 2e as a variable in eq 2. Similarly, with distances and angles (assuming knowledge of the z-axis direction) defined by the reported crystal structure 34 or a suitable DFT-optimized structure, the only variables in eq 3 are T 1e and T 2e .…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

“…The Tpm chemical shifts show slightly less curvature than the corresponding curves for Tp 2 Co over the available temperature range, while our previous work indicated similar levels of contact (isotropic) coupling to the individual protons in the two molecules. 11,14 The one exception was the 3H proton, for which A iso increased sixfold from −0.27 (Tp 2 Co) to −1.5 MHz in the Tpm complex.…”

Section: Apically Appended [Co((tbubzo)tpe) 2 ][Bf 4 ]mentioning

confidence: 99%

Field- and Temperature-Dependent Paramagnetic Relaxation Enhancements in Co(II) Trispyrazolylmethanes

Kumarage,

Marts,

Grindle

et al. 2023

Inorg. Chem.

Self Cite

View full text Add to dashboard Cite

A comprehensive field- and temperature-dependent examination of nuclear magnetic resonance paramagnetic relaxation enhancements (PREs) for the constitutive protons of [Co(Tpm)2][BF4]2 is presented. Data for an apically substituted derivative clearly establish that bis-Tpm complexes of Co(II) undergo Jahn–Teller dynamics about the molecular threefold axis. PREs from the parent Tpm complex were used to numerically extract the electron relaxation times (T 1e). The Tpm complex showed field-dependent behavior, with an approximately 40% higher activation barrier than the related trispyrazolylborate (Tp) complex, based on fits to the T 1e vs T, B 0 data. Analysis of the field-dependent line widths revealed a surprisingly large contribution from susceptibility (Curie) relaxation (20–35% at the highest field), and a molecular radius (9.5 Å) that is consistent with a tightly associated counterion slowing rotation in solution. Density functional theory showed a shared vibration that is consistent with the Jahn–Teller and appears proportionately higher in energy in [Co(Tpm)2]2+. Complete active-space self-consistent field calculations support ascribing electron relaxation to enhanced mixing of the two E g orbital sets that accompanies the tetragonal distortion and the differences in electron correlation times to the higher Jahn–Teller activation barrier in [Co(Tpm)2]2+.

show abstract

Paramagnetic Resonance of Cobalt(II) Trispyrazolylmethanes and Counterion Association

Cited by 8 publications

References 43 publications

Long non‑coding RNA SNHG6 promotes tumorigenesis in melanoma cells via the microRNA‑101‑3p/RAP2B axis

Long non‑coding RNA SNHG6 promotes tumorigenesis in melanoma cells via the microRNA‑101‑3p/RAP2B axis

Spectroscopic and computational studies of reversible O₂ binding by a cobalt complex of relevance to cysteine dioxygenase

Field- and Temperature-Dependent Paramagnetic Relaxation Enhancements in Co(II) Trispyrazolylmethanes

Contact Info

Product

Resources

About

Paramagnetic Resonance of Cobalt(II) Trispyrazolylmethanes and Counterion Association

Cited by 8 publications

References 43 publications

Long non‑coding RNA SNHG6 promotes tumorigenesis in melanoma cells via the microRNA‑101‑3p/RAP2B axis

Long non‑coding RNA SNHG6 promotes tumorigenesis in melanoma cells via the microRNA‑101‑3p/RAP2B axis

Spectroscopic and computational studies of reversible O2 binding by a cobalt complex of relevance to cysteine dioxygenase

Field- and Temperature-Dependent Paramagnetic Relaxation Enhancements in Co(II) Trispyrazolylmethanes

Contact Info

Product

Resources

About

Spectroscopic and computational studies of reversible O₂ binding by a cobalt complex of relevance to cysteine dioxygenase