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1.
J Biochem Mol Toxicol ; 38(2): e23659, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38348706

RESUMO

Circ_0081069 plays a key role in tumor growth; however, its effect on radiosensitivity in esophageal squamous cell carcinoma (ESCC) remains unknown. The study is performed to reveal the association of circ_0081069 expression and radiosensitivity in ESCC and the underlying mechanism. Circ_0081069, miR-195-5p, and spindlin 1 (SPIN1) RNA expression were detected by quantitative real-time polymerase chain reaction. Protein expression was checked by Western blot analysis or immunohistochemistry assay. Cell viability, proliferation, cell apoptosis, migration, and invasion were investigated by cell counting kit-8, 5-Ethynyl-29-deoxyuridine, flow cytometry analysis, scratch test, and transwell assays, respectively. The sensitivity of ESCC cells to radiation was investigated by cell colony formation assay. The interactions among circ_0081069, miR-195-5p, and SPIN1 were identified by dual-luciferase reporter assay and RNA Immunoprecipitation assay. Xenograft mouse model assay was performed to determine the effect of circ_0007841 on radiosensitivity in vivo. Circ_0081069 and SPIN1 expression were upregulated, whereas miR-195-5p was downregulated in ESCC tissues, ESCC cells, and radiation-stimulated ESCC cells. Circ_0081069 silencing inhibited ESCC cell proliferation, invasion, and migration but improved cell apoptosis. In addition, circ_0081069 knockdown enhanced ESCC cell radiosensitivity in vitro and in vivo. Circ_0081069 bound to miR-195-5p and regulated radiosensitivity by binding to miR-195-5p in ESCC cells. Moreover, SPIN1, a target of miR-195-5p, rescued miR-195-5p-mediated effects in ESCC cells. Circ_0081069 was secreted from ESCC cells by being packaged into exosomes. Further, circ_0081069-Exo inhibited radiosensitivity in ESCC cells. Exosome-mediated transfer of circ_0081069 induced SPIN1 production by binding to miR-195-5p, further inhibiting radiosensitivity in ESCC.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Exossomos , MicroRNAs , Humanos , Animais , Camundongos , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/radioterapia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/radioterapia , Transporte Biológico , Modelos Animais de Doenças , MicroRNAs/genética , Proliferação de Células , Linhagem Celular Tumoral
2.
J Biochem Mol Toxicol ; 37(2): e23254, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36426627

RESUMO

BACKGROUND: Breast cancer (BC) is second cancer frequently occurring worldwide. Circular RNA hsa_circ_0000129 (circ_0000129) exerts a tumor-promoting effect in BC. Nevertheless, the molecular mechanisms mediated by the upregulation of circ_0000129 during BC progression are not well understood. METHODS: Forty-five BC patients were recruited for the research. Changes in circ_0000129 levels were detected with quantitative reverse transcription-polymerase chain reaction. Cell proliferation, apoptosis, migration, invasion, and angiopoiesis were determined by cell counting, 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, transwell, and tube formation assays. Protein levels were detected by western blot analysis. The regulatory mechanism of circ_0000129 was predicted by bioinformatics analysis and validated by dual-luciferase reporter and RNA immunoprecipitation assays. In vivo experiments were carried out to verify the function of circ_0000129. RESULTS: Circ_0000129 was overexpressed in BC samples and cell lines. Functionally, circ_0000129 silencing reduced cell proliferation, migration, invasion, and promoted cell apoptosis, as well as induced HUVEC angiopoiesis in vitro. Furthermore, circ_0000129 knockdown decreased BC cell growth in mouse xenograft models. Mechanically, circ_0000129 interacted with miR-485-3p to mediate the inhibiting effect of miR-485-3p on SPIN1. Silenced miR-485-3p expression weakened the inhibiting effect of circ_0000129 knockdown on BC cell malignant behaviors. Also, forced SPIN1 expression weakened miR-485-3p upregulation mediated effects on BC cell malignant behaviors. CONCLUSION: Circ_0000129 acted as a miR-485-3p sponge molecular to mediate expression, thus promoting BC progression.


Assuntos
Neoplasias da Mama , Neoplasias Mamárias Animais , MicroRNAs , Humanos , Animais , Camundongos , Feminino , Neoplasias da Mama/genética , Apoptose , Western Blotting , Proliferação de Células , Modelos Animais de Doenças , MicroRNAs/genética , Linhagem Celular Tumoral
3.
Entropy (Basel) ; 25(5)2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37238471

RESUMO

An analytical solution is obtained for the problem of two interacting, identical but separated spin 1/2 particles in a time-dependent external magnetic field, in a general case. The solution involves isolating the pseudo-qutrit subsystem from a two-qubit system. It is shown that the quantum dynamics of a pseudo-qutrit system with a magnetic dipole-dipole interaction can be described clearly and accurately in an adiabatic representation, using a time-dependent basis set. The transition probabilities between the energy levels for an adiabatically varying magnetic field, which follows the Landau-Majorana-Stuckelberg-Zener (LMSZ) model within a short time interval, are illustrated in the appropriate graphs. It is shown that for close energy levels and entangled states, the transition probabilities are not small and strongly depend on the time. These results provide insight into the degree of entanglement of two spins (qubits) over time. Furthermore, the results are applicable to more complex systems with a time-dependent Hamiltonian.

4.
Entropy (Basel) ; 24(8)2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-36010825

RESUMO

We introduce a quantum version for the statistical complexity measure, in the context of quantum information theory, and use it as a signaling function of quantum order-disorder transitions. We discuss the possibility for such transitions to characterize interesting physical phenomena, as quantum phase transitions, or abrupt variations in correlation distributions. We apply our measure on two exactly solvable Hamiltonian models: the 1D-Quantum Ising Model (in the single-particle reduced state), and on Heisenberg XXZ spin-1/2 chain (in the two-particle reduced state). We analyze its behavior across quantum phase transitions for finite system sizes, as well as in the thermodynamic limit by using Bethe Ansatz technique.

5.
Proc Natl Acad Sci U S A ; 115(25): 6381-6385, 2018 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-29858344

RESUMO

Interferometry is a paradigm for most precision measurements. Using N uncorrelated particles, the achievable precision for a two-mode (two-path) interferometer is bounded by the standard quantum limit (SQL), [Formula: see text], due to the discrete (quanta) nature of individual measurements. Despite being a challenging benchmark, the two-mode SQL has been approached in a number of systems, including the Laser Interferometer Gravitational-Wave Observatory and today's best atomic clocks. For multimode interferometry, the SQL becomes [Formula: see text] using M modes. Higher precision can also be achieved using entangled particles such that quantum noises from individual particles cancel out. In this work, we demonstrate an interferometric precision of [Formula: see text] dB beyond the three-mode SQL, using balanced spin-1 (three-mode) Dicke states containing thousands of entangled atoms. The input quantum states are deterministically generated by controlled quantum phase transition and exhibit close to ideal quality. Our work shines light on the pursuit of quantum metrology beyond SQL.

6.
Molecules ; 26(11)2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34198732

RESUMO

The bipartite entanglement in pure and mixed states of a quantum spin-1 Heisenberg dimer with exchange and uniaxial single-ion anisotropies is quantified through the negativity in a presence of the external magnetic field. At zero temperature the negativity shows a marked stepwise dependence on a magnetic field with two abrupt jumps and plateaus, which can be attributed to the quantum antiferromagnetic and quantum ferrimagnetic ground states. The magnetic-field-driven phase transition between the quantum antiferromagnetic and quantum ferrimagnetic ground states manifests itself at nonzero temperatures by a local minimum of the negativity, which is followed by a peculiar field-induced rise of the negativity observable in a range of moderately strong magnetic fields. The rising temperature generally smears out abrupt jumps and plateaus of the negativity, which cannot be distinguished in the relevant dependencies above a certain temperature. It is shown that the thermal entanglement is most persistent against rising temperature at the magnetic field, for which an energy gap between a ground state and a first excited state is highest. Besides, temperature variations of the negativity of the spin-1 Heisenberg dimer with an easy-axis single-ion anisotropy may exhibit a singular point-kink, at which the negativity has discontinuity in its first derivative. The homodinuclear nickel complex [Ni2(Medpt)2(µ-ox)(H2O)2](ClO4)2·2H2O provides a suitable experimental platform of the antiferromagnetic spin-1 Heisenberg dimer, which allowed us to estimate a strength of the bipartite entanglement between two exchange-coupled Ni2+ magnetic ions on the grounds of the interaction constants reported previously from the fitting procedure of the magnetization data. It is verified that the negativity of this dinuclear compound is highly magnetic-field-orientation dependent due to presence of a relatively strong uniaxial single-ion anisotropy.

7.
J Cell Physiol ; 234(6): 8963-8974, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30317618

RESUMO

Spindlin 1 (SPIN1), which contains Tudor-like domains, regulates maternal transcripts via interaction with a messenger RNA (mRNA)-binding protein. SPIN1 is involved in tumorigenesis in somatic cells and is highly expressed in cancer cells. Nevertheless, the role of SPIN1 in porcine oocyte maturation remains totally unknown. To explore the function of SPIN1 in porcine oocyte maturation, knockdown, and overexpression techniques were used. SPIN1 mRNA was identified in maternal stages ranging from GV to MII. SPIN1 was localized in the cytoplasm and to chromosomes during meiosis. SPIN1 knockdown accelerated first polar body extrusion. Oocytes with overexpressed SPIN1 were arrested at the MI stage. SPIN1 depletion caused meiotic spindle defects and chromosome instability. The BUB3 signal was investigated, confirming that SPIN1 affects the stability of Bub3 mRNA as well as BUB3 expression. Further, overexpression of SPIN1 inhibited the degradation and regulation of G2/mitotic-specific cyclin-B1. In summation, SPIN1 regulates the meiotic cell cycle by modulating the activation of the spindle assembly checkpoint.


Assuntos
Anáfase , Proteínas de Ciclo Celular/metabolismo , Metáfase , Proteínas Associadas aos Microtúbulos/metabolismo , Oócitos/metabolismo , Fosfoproteínas/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Fuso Acromático/metabolismo , Animais , Proteína Quinase CDC2/metabolismo , Proteínas de Ciclo Celular/genética , Células Cultivadas , Segregação de Cromossomos , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Maturação in Vitro de Oócitos , Proteínas Associadas aos Microtúbulos/genética , Fosfoproteínas/genética , Proteínas de Ligação a Poli-ADP-Ribose/genética , Transdução de Sinais , Sus scrofa , Fatores de Tempo
8.
J Cell Biochem ; 120(9): 14562-14572, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31017716

RESUMO

Esophageal squamous cell carcinoma (ESCC) is the most prevalent type in esophageal cancers. Despite accumulating achievements in treatments of ESCC, patients still suffer from recurrence because of the treatment failures, one of the reasons for which is radioresistance. Therefore, it is a necessity to explore the molecular mechanism underlying ESCC radioresistance. Long intergenic noncoding RNA 473 (LINC00473) has been reported to be aberrantly expressed in several human malignancies. However, its biological function in radiosensitivity of ESCC remains to be fully understood. This study explored the role of LINC00473 in radiosensitivity of ESCC cells and whether LINC00473 acted as a competing endogenous RNA to realize its modulation on radioresistance. We found that LINC00473 was markedly upregulated in ESCC tissues and cell lines, and its expression was remarkably related to cellular response to irradiation. In addition, knockdown of LINC00473 could sensitize ESCC cells to radiation in vitro. As for the underlying mechanism, we uncovered that there was a mutual inhibition between LINC00473 and miR-374a-5p. Spindlin1 (SPIN1) was verified as a downstream target of miR-374a-5p, and LINC00473 upregulated SPIN1 expression through negatively modulating miR-374a-5p expression. Furthermore, we revealed that SPIN1 could aggravate the radioresistance of ESCC cells. Finally, overexpression of SPIN1 reversed the LINC00473 silencing-enhanced radiosensitivity in ESCC cells. To sum up, we demonstrated that LINC00473 facilitated radioresistance by regulating the miR-374a-5p/SPIN1 axis in ESCC.


Assuntos
Proteínas de Ciclo Celular/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , MicroRNAs/genética , Proteínas Associadas aos Microtúbulos/genética , Fosfoproteínas/genética , RNA Longo não Codificante/genética , Regiões 3' não Traduzidas , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Prognóstico , Tolerância a Radiação , Regulação para Cima
9.
Biochem Biophys Res Commun ; 505(1): 325-332, 2018 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-30249398

RESUMO

Spindlin1 (SPIN1), a histone modification reader protein, was enriched in the cell nucleolus and facilitated rRNA expression. However, how SPIN1 localizes to the nucleolus and its functional role in rRNA gene expression remain unresolved. Here, we identified a nucleolar localization signal in the N-terminal region of SPIN1 that is essential for its enrichment and function in the nucleolus. We also discovered that, in addition to its H3K4me3 recognizing activity, the H3R8me2a-recognizing capacity of SPIN1 is also indispensable for stimulating rRNA expression. Chromatin immunoprecipitation results indicated that SPIN1 is required for the association or assembly of selective factor 1 (SL1) complex, probably facilitating the initiation of rDNA transcription through its H3 K4me3-R8me2a reader function.


Assuntos
Proteínas de Ciclo Celular/genética , Nucléolo Celular/genética , Expressão Gênica , Genes de RNAr/genética , Histonas/metabolismo , Proteínas Associadas aos Microtúbulos/genética , Fosfoproteínas/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Nucléolo Celular/metabolismo , Imunoprecipitação da Cromatina , Células HEK293 , Células HeLa , Humanos , Metilação , Proteínas Associadas aos Microtúbulos/metabolismo , Fosfoproteínas/metabolismo , Proteínas Pol1 do Complexo de Iniciação de Transcrição/genética , Proteínas Pol1 do Complexo de Iniciação de Transcrição/metabolismo , Ligação Proteica , Interferência de RNA , Transdução de Sinais/genética
10.
Entropy (Basel) ; 20(1)2018 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33265167

RESUMO

For spin-1 condensates, the spatial degrees of freedom can be considered as being frozen at temperature zero, while the spin-degrees of freedom remain free. Under this condition, the entanglement entropy has been derived exactly with an analytical form. The entanglement entropy is found to decrease monotonically with the increase of the magnetic polarization as expected. However, for the ground state in polar phase, an extremely steep fall of the entropy is found when the polarization emerges from zero. Then the fall becomes a gentle descent after the polarization exceeds a turning point.

11.
J Pathol ; 239(4): 459-72, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27171498

RESUMO

Drug resistance is one of the major obstacles for improving the prognosis of breast cancer patients. Increasing evidence has linked the association of aberrantly expressed microRNAs (miRNAs) with tumour development and progression as well as chemoresistance. Despite recent advances, there is still little known about the potential role and mechanism of miRNAs in breast cancer chemoresistance. Here we describe that 16 miRNAs were found to be significantly down-regulated and 11 up-regulated in drug-resistant breast cancer tissues compared with drug-sensitive tissues, using a miRNA microarray. The results also showed miR-489 to be one of the most down-regulated miRNAs in drug-resistant tissues and cell lines, as confirmed by miRNA microarray screening and real-time quantitative PCR. A decrease in miR-489 expression was associated with chemoresistance as well as lymph node metastasis, increased tumour size, advanced pTNM stage and poor prognosis in breast cancer. Functional analysis revealed that miR-489 increased breast cancer chemosensitivity and inhibited cell proliferation, migration and invasion, both in vitro and in vivo. Furthermore, SPIN1, VAV3, BCL2 and AKT3 were found to be direct targets of miR-489. SPIN1 was significantly elevated in drug-resistant and metastatic breast cancer tissues and inversely correlated with miR-489 expression. High expression of SPIN1 was associated with higher histological grade, lymph node metastasis, advanced pTNM stage and positive progesterone receptor (PR) status. Increased SPIN1 expression enhanced cell migration and invasion, inhibited apoptosis and partially antagonized the effects of miR-489 in breast cancer. PIK3CA, AKT, CREB1 and BCL2 in the PI3K-Akt signalling pathway, demonstrated to be elevated in drug-resistant breast cancer tissues, were identified as downstream effectors of SPIN1. It was further found that either inhibition of SPIN1 or overexpression of miR-489 suppressed the PI3K-Akt signalling pathway. These data indicate that miR-489 could reverse the chemoresistance of breast cancer via the PI3K-Akt pathway by targeting SPIN1. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Neoplasias da Mama/metabolismo , Proteínas de Ciclo Celular/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , MicroRNAs/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosfoproteínas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/fisiologia , Apoptose/efeitos dos fármacos , Mama/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Proteínas de Ciclo Celular/genética , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , MicroRNAs/genética , Proteínas Associadas aos Microtúbulos/genética , Pessoa de Meia-Idade , Fosfoproteínas/genética
12.
Artigo em Inglês | MEDLINE | ID: mdl-28130009

RESUMO

Several considerations for the acquisition, processing, and analysis of high quality ultra-wideline (UW) 14N solid-state NMR (SSNMR) powder patterns under static conditions are discussed. It is shown that the 14N quadrupolar parameters may be determined accurately using the frequencies of only two discontinuities in 14N NMR powder patterns that are dominated by the first-order quadrupolar interaction, thereby eliminating the need for the acquisition of the entire pattern and concomitantly reducing experimental time. A framework for utilizing the WURST-CPMG pulse sequence to improve the efficiency of UW 14N SSNMR experiments is explored in two parts: (i) a systematic investigation of the design and parameterization of the WURST pulse is presented, and (ii) the development of the practical aspects of CPMG refocusing for the acquisition of UW 14N SSNMR powder patterns is discussed, with a focus on maximizing both signal-to-noise and resolution, and minimizing spectral distortions. Finally, a strategy is demonstrated that allows for the measurement of the 14N quadrupolar parameters for any nitrogen moiety whose quadrupolar coupling constant falls within the range 0.8≤|CQ|≤1.5MHz, by acquiring only two 14N NMR sub-spectra at strategically located transmitter frequencies; these results are compared to full powder patterns which are acquired using frequency-stepped methods. The methodologies and practical considerations outlined herein are not only useful for the rapid acquisition of UW 14N NMR spectra, but may also be modified and applied for UW NMR of a plethora of quadrupolar and spin-1/2 nuclides.

13.
Nano Lett ; 16(6): 3578-84, 2016 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-27176463

RESUMO

Spin 1/2 honeycomb materials have gained substantial interest due to their exotic magnetism and possible application in quantum computing. However, in all current materials out-of-plane interactions are interfering with the in-plane order, hence a true 2D magnetic honeycomb system is still in demand. Here, we report the exfoliation of the magnetic semiconductor α-RuCl3 into the first halide monolayers and the magnetic characterization of the spin 1/2 honeycomb arrangement of turbostratically stacked RuCl3 monolayers. The exfoliation is based on a reductive lithiation/hydration approach, which gives rise to a loss of cooperative magnetism due to the disruption of the spin 1/2 state by electron injection into the layers. The restacked, macroscopic pellets of RuCl3 layers lack symmetry along the stacking direction. After an oxidative treatment, cooperative magnetism similar to the bulk is restored. The oxidized pellets of restacked single layers feature a magnetic transition at TN = 7 K if the field is aligned parallel to the ab-plane, while the magnetic properties differ from bulk α-RuCl3 if the field is aligned perpendicular to the ab-plane. The deliberate introduction of turbostratic disorder to manipulate the magnetic properties of RuCl3 is of interest for research in frustrated magnetism and complex magnetic order as predicted by the Kitaev-Heisenberg model.

14.
Chemphyschem ; 17(6): 812-6, 2016 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-26699375

RESUMO

The benefits of the ultrafast magic-angle spinning (MAS) approach for the acquisition of ultrawide-line NMR spectra-spectral simplification, increased mass sensitivity allowing the fast study of small amounts of material, efficient excitation, and application to multiple heavy nuclei-are demonstrated for tin(II) oxide (SnO) and the tin complex [(LB)Sn(II) Cl](+) [Sn(II) Cl3 ](-) [LB=2,6-diacetylpyridinebis(2,6-diisopropylanil)] containing two distinct tin environments. The ultrafast MAS experiments provide optimal conditions for the extraction of the chemical-shift anisotropy tensor parameters, anisotropy, and asymmetry for heavy spin-1/2 nuclei.

15.
Magn Reson Chem ; 54(5): 351-7, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26763050

RESUMO

Residual quadrupolar couplings contain important structural information comparable with residual dipolar couplings. However, the measurement of sign and size of especially small residual quadrupolar couplings is difficult. Here, we present an extension of the E.COSY principle to spin systems consisting of a Spin 1 coupled to a spin ½ nucleus, which allows the determination of the sign of the quadrupolar coupling of the Spin 1 nucleus relative to the heteronuclear coupling between the spins. The so-called Q.E.COSY approach is demonstrated with its sign-sensitivity using variable angle NMR, stretched gels and liquid crystalline phases applied to various CD and CD3 groups. Especially the sign-sensitive measurement of residual quadrupolar couplings that remain unresolved in conventional deuterium 1D spectra is shown.

16.
J Mol Cell Biol ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38777743

RESUMO

Spindlin1 (SPIN1) is a unique multivalent histone modification reader that plays a role in ribosomal RNA transcription, chromosome segregation, and tumorigenesis. However, the function of the extended N-terminal region of SPIN1 has remained unclear. Here, we discovered that SPIN1 can form phase-separated and liquid-like condensates both in vitro and in vivo through its N-terminal intrinsically disordered region (IDR). The phase separation of SPIN1 recruits the histone methyltransferase MLL1 to the same condensates and enriches the H3K4 methylation marks. This process also facilitates the binding of SPIN1 to H3K4me3 and activates tumorigenesis-related genes. Moreover, SPIN1-IDR enhances the genome-wide chromatin binding of SPIN1 and facilitates its localization to genes associated with the MAPK signaling pathway. These findings provide new insights into the biological function of the IDR in regulating SPIN1 activity and reveal a previously unrecognized role of SPIN1-IDR in histone methylation readout. Our study uncovers the crucial role of appropriate biophysical properties of SPIN1 in facilitating gene expression and links phase separation to tumorigenesis, which provides a new perspective for understanding the function of SPIN1.

17.
Pathol Res Pract ; 241: 154216, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36459832

RESUMO

BACKGROUND: Abnormal expression of circular RNAs (circRNAs) plays an important role in tumorigenesis and radiosensitivity of many cancers. Nevertheless, it is not clear whether circ_0001686 is associated with the development and radiosensitivity of esophagus cancer. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of circ_0001686, microRNA-876-5p (miR-876-5p) and spindlin 1 (SPIN1). Counting Kit-8 (CCK-8) assay, EdU assay, flow cytometry and transwell assay were applied to evaluate cell viability, cell proliferation, cell apoptosis and cell invasion capacities. Radiosensitivity was monitored by colony formation assay. The target relationship between miR-876-5p and circ_0001686 or SPIN1 was identified by dual-luciferase reporter assay. The protein level of SPIN1 was measured by western blot assay. Xenograft tumor models were used to analyze the influence of circ_0001686 on radiosensitivity and tumor growth in vivo. RESULTS: The expression levels of circ_0001686 and SPIN1 were increased, while miR-876-5p was decreased in esophagus cancer tissues and cells. Interference of circ_0001686 constrained cell proliferation and invasion, but promoted cell apoptosis and radiosensitivity. Additionally, miR-876-5p was the target of circ_0001686 and miR-876-5p inhibition effectively ameliorated the impacts of circ_0001686 deficiency on tumorigenesis and radiosensitivity. Moreover, SPIN1 was a direct target of miR-876-5p and SPIN1 overexpression partially overturned the effects of miR-876-5p transfection on tumor progression and radiosensitivity. Importantly, circ_0001686 could sponge miR-876-5p to regulate SPIN1 expression. In addition, circ_0001686 silencing also constrained tumor growth and increased radiosensitivity in vivo. CONCLUSION: Circ_0001686 contributed to the progression and radioresistance of esophagus cancer cells via regulating SPIN1 expression by targeting miR-876-5p, providing a new therapeutic target for improving the prognosis of esophagus cancer patients.


Assuntos
Neoplasias Esofágicas , MicroRNAs , Humanos , Animais , Carcinogênese/genética , Transformação Celular Neoplásica , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/radioterapia , Apoptose/genética , Proliferação de Células/genética , Modelos Animais de Doenças , MicroRNAs/genética
18.
J Mol Biol ; 435(6): 167993, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36736887

RESUMO

Heterogeneous nuclear ribonucleoprotein K (HNRNPK, hnRNP K), a multifunctional RNA/DNA binding protein, mainly regulates transcription, translation and RNA splicing, and then plays oncogenic roles in many cancers. However, the related mechanisms remain largely unknown. Here, we found that HNRNPK can partially epigenetically regulate cancer cell proliferation via increasing transcription and exon 4-inclusion of SPIN1, an important oncogenic histone code reader. This exon 4 skipping event of SPIN1 generates a long non-coding RNA, followed by the downregulation of SPIN1 protein. SPIN1 is one of the most significantly co-expressed genes of HNRNPK in thirteen TCGA cancers. Our further studies revealed HNRNPK knockdown significantly inhibited cell growth and cell cycle progression in oral squamous cell carcinoma (OSCC) cells and promoted cell apoptosis. Overexpression of SPIN1 was able to partially rescue the growth inhibition triggered by HNRNPK knockdown. Moreover, CCND1 (Cyclin D1), a key cell cycle regulator and oncogene, epigenetically up-regulated by SPIN1, was also positively regulated by HNRNPK. In addition, we discovered that HNRNPK promoted SPIN1 exon 4 inclusion by interacting with an intronic splicing enhancer in intron 4. Collectively, our study suggests a novel epigenetic regulatory pathway of HNRNPK in OSCC, mediated by controlling the transcription activity and alternative splicing of SPIN1 gene.


Assuntos
Carcinoma de Células Escamosas , Proteínas de Ciclo Celular , Epigênese Genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo K , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Ciclo Celular/genética , Proliferação de Células/genética , Éxons/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo K/genética , Código das Histonas/genética , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Proteínas de Ciclo Celular/genética
19.
J Phys Condens Matter ; 35(45)2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37553001

RESUMO

We have investigated magnetic phase diagrams of spin-crossover (SCO) solids throughout the Blume-Emery-Griffiths spin-1 model where the spin states ±1 and 0 are associated to high-spin state and low-spin states respectively. In the present work, the quadrupolar interaction,K, parameter depends linearly on temperature and accounts for the role of the lattice phonons in the elastic interactions between the SCO units. Magnetic interactions are randomly distributed in the system and are controlled by a factorγ=Jij/Ksuch that forγ = 0 (Jij=0), magnetic ordering is not expected. The crystal-field that acts on SCO sites depends both on the ligand-field strength and the degeneracy ratio between HS and LS states as in some previous works. The system is also under the effect of a random local magnetic fieldhiacting on each sitei. The model is solved using a homogeneous mean field theory. Our investigations reveal the occurrence of thermally-induced gradual, and first-order spin-transitions by varying the model parameters. At vicinity of first-order transition, various types of isothermal magnetic hysteresis loops are obtained and their corresponding coercive field and loop patterns are discussed as function of temperature.

20.
J Phys Condens Matter ; 35(11)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36599166

RESUMO

Frustration-driven quantum fluctuation leads to many exotic phases in the ground state (GS) and the study of these quantum phase transitions is one of the most challenging areas of research in condensed matter physics. We study a frustrated HeisenbergJ1-J2model of spin-1/2 chain with nearest exchange interactionJ1and next nearest exchange interactionJ2using the principal component analysis (PCA) which is an unsupervised machine learning technique. In this method most probable spin configurations (MPSCs) of GS and first excited state (FES) for differentJ2/J1are used as the input in PCA to construct the covariance matrix. The 'quantified principal component'p1(J2/J1)of the largest eigenvalue of the covariance matrix is calculated and it is shown that the nature and variation ofp1(J2/J1)can accurately predict the phase transitions and degeneracies in the GS. Thep1(J2/J1)calculated from the MPSC of GS only exhibits the signature of degeneracies in the GS, whereas,p1(J2/J1)calculated from the MPSC of FES captures the gapless spin liquid (GSL)-dimer phase transition as well as all the degeneracies of the model system. We show that the jump inp1(J2/J1)of FES atJ2/J1≈0.241, indicates the GSL-dimer phase transition, whereas its kinks give the signature of the GS degeneracies. The scatter plot of the first two principal components of FES shows distinct band formation for different phases. The MPSCs are obtained by using an iterative variational method (IVM) which gives the approximate eigenvalues and eigenvectors.

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