Annexin A1 in Malignant Tumors: Current Opinions and                     Controversies

Annexin A1 is a 37 kDa calcium and phospholipid-binding protein that participates in several biological processes, such as inflammatory reactions, modulation of cell proliferation, regulation of cell death signaling, apoptosis, and, most importantly, tumor formation and development. Although annexin A1 has been implicated in the biology of various tumors, the findings are highly controversial and information regarding the underlying mechanism remains limited. Moreover, the mechanism by which annexin A1 participates in carcinogenesis and tumor progression is rather unclear. In the current study, we review the important biological functions of annexin A1 in different tumors. This work indicates that annexin A1 is a possible target for novel therapeutic intervention and that it is a potential biomarker for tumor diagnosis and screening.

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Research Progress of miRNA Regulating Cell Signaling Pathways Related to Hepatocarcinogenesis

Journal of Clinical and Nursing Research ◽

10.26689/jcnr.v5i2.1921 ◽

2021 ◽

Vol 5 (2) ◽

Author(s):

Dan Wang ◽

Xingwu Yang ◽

Guotai Wang

Keyword(s):

Signaling Pathways ◽

Target Genes ◽

Malignant Tumors ◽

Research Progress ◽

Biological Processes ◽

Tumor Cell Proliferation ◽

Invasion And Metastasis ◽

Diagnosis And Prognosis ◽

Potential Biomarker ◽

Cell Signaling Pathways

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in clinical practice. The pathogenesis of HCC is still unclear. Currently, the clinical treatment of HCC is poorly targeted and the therapeutic effect is poor. MicroRNAs (miRNAs) are closely related to the occurrence of HCC, and they are mainly involved in the occurrence and development of HCC through binding to target genes or acting on related signaling pathways. In recent years, studies have shown that miRNA can be used as a potential biomarker for diagnosis and prognosis of HCC. In addition, studies have also shown that miRNA plays a tumor-suppressing or tumor-promoting role in the process of HCC by regulating the biological processes of tumor cell proliferation, migration, invasion and metastasis. In this paper, the recent studies on miRNA signaling pathways related to the occurrence and development of HCC were reviewed, with a view to providing ideas for the clinical diagnosis and treatment of HCC.

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USP1 Promotes GC Metastasis via Stabilizing ID2

Disease Markers ◽

10.1155/2021/3771990 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Nuoya Li ◽

Lei Wu ◽

Xingye Zuo ◽

Huilong Luo ◽

Yanling Sheng ◽

...

Keyword(s):

Malignant Tumors ◽

Survival Rates ◽

Underlying Mechanism ◽

Poor Survival ◽

Cellular Analysis ◽

Potential Biomarker ◽

Therapy Target

Gastric cancer (GC) is one of the most common malignant tumors all over the world. And recurrence and metastasis are still the main causes of low survival rate for advanced GC. USP1 has been shown overexpressed in multiple cancers, which indicate its important biomarker in tumorigenesis and development. Our study is aimed at defining the exact role of USP1 on GC metastasis and the underlying mechanism. USP1 was firstly found overexpressed in GC tissues and relatively high-expression levels conferred poor survival rates. Then, real-time cellular analysis (RTCA) showed that USP1 knockdown inhibited GC metastasis both in vitro and in vivo. Mechanically, we demonstrated that USP1 promoted GC metastasis via upregulating ID2 expression and further confirmed that USP1 stabilized ID2 expression through deubiquitinating ID2 in GC. In conclusion, our study showed that USP1 promoted GC metastasis via stabilizing ID2 expression, which provides a potential biomarker and therapy target for GC.

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The role and underlying mechanism of miR-1299 in cancer

Future Science OA ◽

10.2144/fsoa-2021-0014 ◽

2021 ◽

pp. FSO693

Author(s):

Deng Kaiyuan ◽

Huang Lijuan ◽

Sun Xueyuan ◽

Zang Yunhui

Keyword(s):

Cell Proliferation ◽

Tumor Suppressor ◽

Target Genes ◽

Biological Activities ◽

Underlying Mechanism ◽

Biological Processes ◽

Biological Functions ◽

Disease Mechanisms ◽

Evolutionarily Conserved ◽

New Perspective

A type of evolutionarily conserved, noncoding, small, endogenous, single-stranded RNA, miRNAs are widely distributed in eukaryotes, where they participate in various biological processes as critical regulatory molecules. miR-1299 has mainly been investigated in cancers. miR-1299 is a tumor suppressor that regulates the expression of its target genes, activating or inhibiting the transcription of genes regulating biological activities including cell proliferation, migration, survival and programmed cell death. miR-1299 has become a hotspot in research of disease mechanisms and biomarkers; elucidation of the regulatory roles of miR-1299 in tumorigenesis, proliferation, apoptosis, invasion, migration and angiogenesis may provide a new perspective for understanding its biological functions as a tumor suppressor.

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Comparison and Analysis of Computational Methods for Identifying N6 - methyladenosine Sites in Saccharomyces Cerevisiae

Current Pharmaceutical Design ◽

10.2174/1381612826666201109110703 ◽

2020 ◽

Vol 26 ◽

Author(s):

Pengmian Feng ◽

Lijing Feng ◽

Chaohui Tang

Keyword(s):

Saccharomyces Cerevisiae ◽

Computational Methods ◽

Computational Analysis ◽

Computational Prediction ◽

Experimental Methods ◽

Biological Processes ◽

Biological Functions ◽

Precise Location ◽

Future Directions ◽

The Past

Background and Purpose: N 6 -methyladenosine (m6A) plays critical roles in a broad set of biological processes. Knowledge about the precise location of m6A site in the transcriptome is vital for deciphering its biological functions. Although experimental techniques have made substantial contributions to identify m6A, they are still labor intensive and time consuming. As good complements to experimental methods, in the past few years, a series of computational approaches have been proposed to identify m6A sites. Methods: In order to facilitate researchers to select appropriate methods for identifying m6A sites, it is necessary to give a comprehensive review and comparison on existing methods. Results: Since researches on m6A in Saccharomyces cerevisiae are relatively clear, in this review, we summarized recent progresses on computational prediction of m6A sites in S. cerevisiae and assessed the performance of existing computational methods. Finally, future directions of computationally identifying m6A sites were presented. Conclusion: Taken together, we anticipate that this review will provide important guides for computational analysis of m 6A modifications.

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Annexin-A1 SUMOylation regulates microglial polarization after cerebral ischemia by modulating IKKα stability via selective autophagy

Science Advances ◽

10.1126/sciadv.abc5539 ◽

2021 ◽

Vol 7 (4) ◽

pp. eabc5539

Author(s):

Xing Li ◽

Qian Xia ◽

Meng Mao ◽

Huijuan Zhou ◽

Lu Zheng ◽

...

Keyword(s):

Cerebral Ischemia ◽

Underlying Mechanism ◽

Nuclear Factor Κb ◽

Annexin A1 ◽

Selective Autophagy ◽

Microglial Polarization ◽

Proinflammatory Mediators ◽

Therapeutic Benefits ◽

Iκb Kinase ◽

Ikk Complex

Annexin-A1 (ANXA1) has recently been proposed to play a role in microglial activation after brain ischemia, but the underlying mechanism remains poorly understood. Here, we demonstrated that ANXA1 is modified by SUMOylation, and SUMOylated ANXA1 could promote the beneficial phenotype polarization of microglia. Mechanistically, SUMOylated ANXA1 suppressed nuclear factor κB activation and the production of proinflammatory mediators. Further study revealed that SUMOylated ANXA1 targeted the IκB kinase (IKK) complex and selectively enhanced IKKα degradation. Simultaneously, we detected that SUMOylated ANXA1 facilitated the interaction between IKKα and NBR1 to promote IKKα degradation through selective autophagy. Further work revealed that the overexpression of SUMOylated ANXA1 in microglia/macrophages resulted in marked improvement in neurological function in a mouse model of cerebral ischemia. Collectively, our study demonstrates a previously unidentified mechanism whereby SUMOylated ANXA1 regulates microglial polarization and strongly indicates that up-regulation of ANXA1 SUMOylation in microglia may provide therapeutic benefits for cerebral ischemia.

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Transcriptome Analysis Provides Insights into the Mechanism of Astaxanthin Enrichment in a Mutant of the Ridgetail White Prawn Exopalaemon carinicauda

Genes ◽

10.3390/genes12050618 ◽

2021 ◽

Vol 12 (5) ◽

pp. 618

Author(s):

Yue Jin ◽

Shihao Li ◽

Yang Yu ◽

Chengsong Zhang ◽

Xiaojun Zhang ◽

...

Keyword(s):

Transcriptome Analysis ◽

Underlying Mechanism ◽

Biological Processes ◽

Wild Type ◽

Expression Levels ◽

In The Wild ◽

Cuticle Proteins ◽

Apolipoprotein D ◽

High Level ◽

Lower Expression

A mutant of the ridgetail white prawn, which exhibited rare orange-red body color with a higher level of free astaxanthin (ASTX) concentration than that in the wild-type prawn, was obtained in our lab. In order to understand the underlying mechanism for the existence of a high level of free astaxanthin, transcriptome analysis was performed to identify the differentially expressed genes (DEGs) between the mutant and wild-type prawns. A total of 78,224 unigenes were obtained, and 1863 were identified as DEGs, in which 902 unigenes showed higher expression levels, while 961 unigenes presented lower expression levels in the mutant in comparison with the wild-type prawns. Based on Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes analysis, as well as further investigation of annotated DEGs, we found that the biological processes related to astaxanthin binding, transport, and metabolism presented significant differences between the mutant and the wild-type prawns. Some genes related to these processes, including crustacyanin, apolipoprotein D (ApoD), cathepsin, and cuticle proteins, were identified as DEGs between the two types of prawns. These data may provide important information for us to understand the molecular mechanism of the existence of a high level of free astaxanthin in the prawn.

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Beneficial Actions of Orostachys japonica and Its Compounds against Tumors via MAPK Signaling Pathways

Nutrients ◽

10.3390/nu13020555 ◽

2021 ◽

Vol 13 (2) ◽

pp. 555

Author(s):

Soyoung Hur ◽

Eungyeong Jang ◽

Jang-Hoon Lee

Keyword(s):

Molecular Mechanisms ◽

Epithelial To Mesenchymal Transition ◽

Malignant Tumors ◽

Treatment Options ◽

Underlying Mechanism ◽

Mapk Signaling ◽

Mitogen Activated Protein Kinase ◽

Antitumor Effects ◽

Mesenchymal Transition ◽

Perennial Plant

Tumors are one of the most life-threatening diseases, and a variety of cancer treatment options have been continuously introduced in order to overcome cancer and improve conventional therapy. Orostachys japonica (O. japonica), which is a perennial plant belonging to the genus Orostachys of the Crassulaceae family, has been revealed to exhibit pharmacological properties against various tumors in numerous studies. The present review aimed to discuss the biological actions and underlying molecular mechanisms of O. japonica and its representative compounds—kaempferol and quercetin—against tumors. O. japonica reportedly has antiproliferative, anti-angiogenic, and antimetastatic activities against various types of malignant tumors through the induction of apoptosis and cell cycle arrest, a blockade of downstream vascular endothelial growth factor (VEGF)-VEGFR2 pathways, and the regulation of epithelial-to-mesenchymal transition. In addition, emerging studies have highlighted the antitumor efficacy of kaempferol and quercetin. Interestingly, it was found that alterations of the mitogen-activated protein kinase (MAPK) signaling cascades are involved in the pivotal mechanisms of the antitumor effects of O. japonica and its two compounds against cancer cell overgrowth, angiogenesis, and metastasis. In summary, O. japonica could be considered a preventive and therapeutic medicinal plant which exhibits antitumor actions by reversing altered patterns of MAPK cascades, and kaempferol and quercetin might be potential components that can contribute to the efficacy and underlying mechanism of O. japonica.

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lncRNA CASC19 Contributes to Radioresistance of Nasopharyngeal Carcinoma by Promoting Autophagy via AMPK-mTOR Pathway

International Journal of Molecular Sciences ◽

10.3390/ijms22031407 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1407

Author(s):

Hongxia Liu ◽

Wang Zheng ◽

Qianping Chen ◽

Yuchuan Zhou ◽

Yan Pan ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Cell Line ◽

Malignant Tumors ◽

Underlying Mechanism ◽

Mtor Pathway ◽

Rna Seq ◽

Cellular Autophagy ◽

First Time

Nasopharyngeal carcinoma (NPC) is one of the most frequent head and neck malignant tumors and is majorly treated by radiotherapy. However, radiation resistance remains a serious obstacle to the successful treatment of NPC. The aim of this study was to discover the underlying mechanism of radioresistance and to elucidate novel genes that may play important roles in the regulation of NPC radiosensitivity. By using RNA-seq analysis of NPC cell line CNE2 and its radioresistant cell line CNE2R, lncRNA CASC19 was screened out as a candidate radioresistance marker. Both in vitro and in vivo data demonstrated that a high expression level of CASC19 was positively correlated with the radioresistance of NPC, and the radiosensitivity of NPC cells was considerably enhanced by knockdown of CASC19. The incidence of autophagy was enhanced in CNE2R in comparison with CNE2 and another NPC cell line HONE1, and silencing autophagy with LC3 siRNA (siLC3) sensitized NPC cells to irradiation. Furthermore, CASC19 siRNA (siCASC19) suppressed cellular autophagy by inhibiting the AMPK/mTOR pathway and promoted apoptosis through the PARP1 pathway. Our results revealed for the first time that lncRNA CASC19 contributed to the radioresistance of NPC by regulating autophagy. In significance, CASC19 might be a potential molecular biomarker and a new therapeutic target in NPC.

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Preclinical activity of cobimetinib alone or in combination with chemotherapy and targeted therapies in renal cell carcinoma

Future Oncology ◽

10.2217/fon-2021-0256 ◽

2021 ◽

Author(s):

Lichen Zhang ◽

Deqiong Xie ◽

Yonghua Lei ◽

Aoli Na ◽

Lei Zhu

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Mapk Pathway ◽

Standard Of Care ◽

Underlying Mechanism ◽

Mek Inhibitor ◽

Tumor Formation ◽

Pathway Inhibition ◽

New Treatments

Background: The poor outcome of advanced renal cell carcinoma (RCC) necessitates new treatments. Cobimetinib is a MEK inhibitor and approved for the treatment of melanoma. This work investigated the efficacy of cobimetinib alone and in combination with anti-RCC drugs. Methods: Proliferation and apoptosis assays were performed, and combination index was analyzed on RCC cell lines (CaKi-2, 786-O, A-704, ACHN and A489) and xenograft models. Immunoblotting analysis was conducted to investigate the MAPK pathway. Results: Cobimetinib was active against RCC cells, with IC50 at 0.006–0.8μM, and acted synergistically with standard-of-care therapy. Cobimetinib at nontoxic doses prevented tumor formation, inhibited tumor growth and enhanced efficacy of 5-fluorouracil, sorafenib and sunitinib via suppressing Raf/MEK/ERK, leading to MAPK pathway inhibition. Conclusion: Our findings demonstrate the potent anti-RCC activity of cobimetinib and its synergism with RCC standard-of-care drugs, and confirm the underlying mechanism of the action of cobimetinib.

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Semiautomated 3D mapping of aneurysmal wall enhancement with 7T-MRI

Scientific Reports ◽

10.1038/s41598-021-97727-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ashrita Raghuram ◽

Alberto Varon ◽

Jorge A. Roa ◽

Daizo Ishii ◽

Yongjun Lu ◽

...

Keyword(s):

Intracranial Aneurysms ◽

3D Imaging ◽

High Resolution Imaging ◽

Biological Processes ◽

Automated Method ◽

Aneurysm Wall ◽

Unruptured Intracranial Aneurysms ◽

Potential Biomarker ◽

Resolution Imaging ◽

Objective Tool

AbstractAneurysm wall enhancement (AWE) after the administration of contrast gadolinium is a potential biomarker of unstable intracranial aneurysms. While most studies determine AWE subjectively, this study comprehensively quantified AWE in 3D imaging using a semi-automated method. Thirty patients with 33 unruptured intracranial aneurysms prospectively underwent high-resolution imaging with 7T-MRI. The signal intensity (SI) of the aneurysm wall was mapped and normalized to the pituitary stalk (PS) and corpus callosum (CC). The CC proved to be a more reliable normalizing structure in detecting contrast enhancement (p < 0.0001). 3D-heatmaps and histogram analysis of AWE were used to generate the following metrics: specific aneurysm wall enhancement (SAWE), general aneurysm wall enhancement (GAWE) and focal aneurysm wall enhancement (FAWE). GAWE was more accurate in detecting known morphological determinants of aneurysm instability such as size ≥ 7 mm (p = 0.049), size ratio (p = 0.01) and aspect ratio (p = 0.002). SAWE and FAWE were aneurysm specific metrics used to characterize enhancement patterns within the aneurysm wall and the distribution of enhancement along the aneurysm. Blebs were easily identified on 3D-heatmaps and were more enhancing than aneurysm sacs (p = 0.0017). 3D-AWE mapping may be a powerful objective tool in characterizing different biological processes of the aneurysm wall.

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