Hepatocellular carcinoma (HCC) is the most common primary liver cancer with a dismal prognosis, especially when diagnosed at advanced stages. Annexin A2 (ANXA2), is found to promote cancer progression and therapeutic resistance. However, the underlining mechanisms of ANXA2 in immune escape of HCC remain poorly understood up to now. Herein, we summarized the molecular function of ANXA2 in HCC and its relationship with prognosis. Furthermore, we tentatively elucidated the underlying mechanism of ANXA2 immune escape of HCC by upregulating the proportion of regulatory T cells and the expression of several inhibitory molecules, and by downregulating the proportion of natural killer cells and dendritic cells and the expression of several inhibitory molecules or effector molecules. We expect a lot of in-depth studies to further reveal the underlying mechanism of ANXA2 in immune escape of HCC in the future.

Annexin A2 promotion of hepatocellular carcinoma tumorigenesis via the immune microenvironment

The in vivo fate and targeting engineering of crossover vesicle-based gene delivery system.

To investigate the effects of lncRNA MIR155HG and Annexin A2 (ANXA2) on colorectal cancer (CRC) and the mechanism of the MIR155HG/ANXA2 axis. The expressions of MIR155HG and ANXA2 in human CRC tissues were analyzed for association with pathological characteristics and prognosis of CRC patients. CRC cell lines (Caco2 and HT29) were used to study the effects of MIR155HG or ANXA2 knockdown on tumor cell behaviors and macrophage polarization as well as the effect of M2 polarization on oxaliplatin resistance of CRC cells. RNA immunoprecipitation, RNA pull-down and dual-luciferase reporter assays were applied to verify the targeting relationships among MIR155HG, miR-650 and ANXA2. Heterotopic xenograft models were established to verify the results of cell experiments. MIR155HG and ANXA2 were highly expressed in CRC tissues/cells and of prognostic values for CRC patients. Knockdown of MIR155HG or ANXA2 suppressed M2 macrophage polarization, and proliferation, migration, invasion and oxaliplatin resistance of CRC cells. MIR155HG competed with ANXA2 for binding miR-650 and can also directly target ANXA2. Knockdown of MIR155HG or ANXA2 also inhibited M2 macrophage polarization and CRC progression in nude mice. This study highlighted that MIR155HG, by regulating the miR-650/ANXA2 axis, promotes CRC progression and enhances oxaliplatin resistance in CRC cells through M2 macrophage polarization.

LncRNA MIR155HG induces M2 macrophage polarization and drug resistance of colorectal cancer cells by regulating ANXA2

Phage display is an effective and powerful technique that provides a route to discovery unique peptides targeting to tumor cells. Specifically binding peptides are considered as the valuable target directing molecule fragments with potential efficiency to improve the current tumor clinic, and offer new approaches for tumor prevention, diagnosis and treatment. We focus on the recent advances in the isolation of tumor-targeting peptides by biopanning methods, with particular emphasis on molecular imaging, and pharmaceutical targeting therapy.

/pdf/application-of-phage-displayed-peptides-in-tumor-imaging-19i60d09gp.pdf

Application of Phage-Displayed Peptides in Tumor Imaging Diagnosis and Targeting Therapy.

Medulloblastomas (MBs) and glioblastomas (GBMs) are high-incidence central nervous system tumors. Different origin sites and changes in the tissue microenvironment have been associated with the onset and progression. Here, we describe differences between the extracellular matrix (ECM) signatures of these tumors. We compared the proteomic profiles of MB and GBM decellularized tumor samples between each other and their normal decellularized brain site counterparts. Our analysis revealed that 19, 28, and 11 ECM proteins were differentially expressed in MBs, GBMs, and in both MBs and GBMs, respectively. Next, we validated key findings by using a protein tissue array with 53 MB and 55 GBM cases and evaluated the clinical relevance of the identified differentially expressed proteins through their analysis on publicly available datasets, 763 MB samples from the GSE50161 and GSE85217 studies, and 115 GBM samples from RNAseq-TCGA. We report a shift toward a denser fibrillary ECM as well as a clear alteration in the glycoprotein signature, which influences the tumor pathophysiology. MS data have been submitted to the PRIDE repository, project accession: PXD023350.

Extracellular Matrix Proteome Remodeling in Human Glioblastoma and Medulloblastoma.

'Targeting peptides' have demonstrated their value in diagnostic imaging and therapy and novel peptide probes specific to cervical cancer were developed. In the M13KE phage dodecapeptide (12-mer) peptide library, the phage clone S7 showed the best binding to the cancer cells as confirmed by immunofluorescence and flow cytometry assays, and was selected for continued studies. Its binding peptide, CSP3, was synthesized from the sequence of S7's 12-mer at the N-terminus of the minor coat protein pIII of this M13KE phage vector. The peptide's binding was analyzed by the same assays used for S7. It was also assessed using competitive inhibition and binding to a tissue chip. The results demonstrated that the CSP3 peptide bound to cervical carcinoma cells with high sensitivity and specificity. The positive results indicated that the peptide CSP3, conjugated with nanomaterials and chemotherapeutics, may be developed as a targeting vehicle for therapeutic drug delivery against cervical cancer, especially cervical cancer with multiple drug resistance. For this aim, we prepared a CSP3 conjugated liposome drug delivery system containing doxorubicin (DOX) and microRNA101 (miR101) expression plasmids (CSP3-Lipo-DOX-miR101), and the primary result showed that the system demonstrated significantly enhanced cytotoxicity to SiHa cells and DOX resistant SiHa cells, SiHa/ADR. Our results showed that CSP3 is a cervical cancer targeting 12aa peptide with high specificity and sensitivity, and the CSP3 conjugated drug delivery system, CSP3-Lipo-DOX-miR101 has promising potential for development as an efficient drug system for the therapy of cervical cancer.

https://iopscience.iop.org/article/10.1088/1361-6528/aaf3f8/pdf

Development of a novel drug targeting delivery system for cervical cancer therapy

Annexin A2 (ANXA2) is reported to be associated with cancer development. To investigate the roles ANXA2 plays during the development of cancer, the RNAi method was used to inhibit the ANXA2 expression in caco2 (human colorectal cancer cell line) and SMMC7721 (human hepatocarcinoma cell line) cells. The results showed that when the expression of ANXA2 was efficiently inhibited, the growth and motility of both cell lines were significantly decreased, and the development of the motility relevant microstructures, such as pseudopodia, filopodia, and the polymerization of microfilaments and microtubules were obviously inhibited. The cancer cell apoptosis was enhanced without obvious significance. The possible regulating pathway in the process was also predicted and discussed. Our results suggested that ANXA2 plays important roles in maintaining the malignancy of colorectal and hepatic cancer by enhancing the cell proliferation, motility, and development of the motility associated microstructures of cancer cells based on a possible complicated signal pathway.

/pdf/annexin-a2-enhances-the-progression-of-colorectal-cancer-and-eall2hi5ji.pdf

Ruiye Zuo

Papers

Development of a novel drug targeting delivery system for cervical cancer therapy

Annexin A2 Enhances the Progression of Colorectal Cancer and Hepatocarcinoma via Cytoskeleton Structural Rearrangements.