miR-12 Derived from Bone Marrow Mesenchymal Stem Cells Accelerates the Development of Human Papillomavirus by Up-Regulating AN1

The miRNA derived from Bone marrow mesenchymal stem cells (BMSCs) have crucial effects on tumors. The tumor could be affected by the abnormal expression of miRNA in human papillomavirus (HPV). Our study aimed to identify the potential brand-new biomarker in order to reveal the pathogenesis of HPV. miRNA derived from BMSCs was detected and identified. The action of miR-12 on biological behavior of HPV was detected. The level of AN1 protein was detected by Western-blot and IHC method. The relationship between miR-12 and AN1 was assessed by bioinformatics analysis and luciferase assay. The tumor cell biological behaviors were evaluated by manipulating miR12 and AN1 level. The tumor volume derived from BMSCs was diminished significantly compared with normal tissues. The tumor volume was bigger after combined injection with Hela cell and miR-12 compared with single injection. The cell proliferative and invasive ability was strengthened after transfection with miR-12mimics. The cell invasive ability was reduced significantly after transfection of si-miR-12. AN1 was a target gene of miR-12 as confirmed by the analysis on bioinformatics and luciferase activity. The phenotype was reversed after the silent presentation of AN1 was disturbed. In conclusion, miR-12 expression is elevated in HPV cells and affects HPV cells through targeting the AN1 signaling pathway.

RhoGDI2-Mediated Rac1 Recruitment to Filamin A Enhances Rac1 Activity and Promotes Invasive Abilities of Gastric Cancer Cells

Rho GDP dissociation inhibitor 2 (RhoGDI2), a regulator of Rho family GTPase, has been known to promote tumor growth and malignant progression in gastric cancer. We previously showed that RhoGDI2 positively regulates Rac1 activity and Rac1 activation is critical for RhoGDI2-induced gastric cancer cell invasion. In this study, to identify the precise molecular mechanism by which RhoGDI2 activates Rac1 activity, we performed two-hybrid screenings using yeast and found that RhoGDI2 plays an important role in the interaction between Rac1, Filamin A and Rac1 activation in gastric cancer cells. Moreover, we found that Filamin A is required for Rac1 activation and the invasive ability of gastric cancer cells. Depletion of Filamin A expression markedly reduced Rac1 activity in RhoGDI2-expressing gastric cancer cells. The migration and invasion ability of RhoGDI2-expressing gastric cancer cells also substantially decreased when Filamin A expression was depleted. Furthermore, we found that Trio, a Rac1-specific guanine nucleotide exchange factor (GEF), is critical for Rac1 activation and the invasive ability of gastric cancer cells. Therefore, we conclude that RhoGDI2 increases Rac1 activity by recruiting Rac1 to Filamin A and enhancing the interaction between Rac1 and Trio, which is critical for the invasive ability of gastric cancer cells.

Protein Arginine Methyltransferase 5 Promotes the Migration of AML Cells by Regulating the Expression of Leukocyte Immunoglobulin-Like Receptor B4

Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults with poor prognosis. Especially for AML-M5 type, due to the strong cell migration ability, the possibility of extramedullary invasion is large and widespread, which leads to poor therapeutic effect. Previous studies have found that protein arginine methyltransferase 5 (PRMT5) could promote the proliferation and differentiation of leukemic cells in AML, but its regulation on the invasive ability of AML cells remains unclear. This study was designed to explore the role of PRMT5 in regulating the invasion of AML cells and to investigate the mechanisms. Patient samples were collected for detection of PRMT5 expression level. AML cells were used for exploring the function of PRMT5. The results of clinical samples showed that the expression of PRMT5 was significantly increased in newly diagnosed and recurrent AML patients, and the expression of leukocyte immunoglobulin-like receptor B4 (LILRB4) was positively correlated with the level of PRMT5. In the cell experiment in vitro, we found that when PRMT5 was knocked down, the invasion, migration, and adhesion capacities of MV-4-11 cells and THP-1 cells were decreased, and the mRNA and protein levels of LILRB4 were also decreased. Moreover, we screened related signaling pathways and found that PRMT5 affected the expression of downstream LILRB4 by activating mTOR pathway, which in turn enhanced the invasive ability of AML cells. Taken together, PRMT5 plays an important role in the invasion of AML, which acts via regulating the expression of LILRB4. PRMT5 could act as a potential therapeutic candidate for AML.

SYDE1 Acts as an Oncogene in Glioma and has Diagnostic and Prognostic Values

Objectives: Gliomas remain one of serious public health problems worldwide which demand further and deeper investigation. The aim of this study was to explore the association between synapse defective protein 1 homolog 1 (SYDE1) and gliomas via public database analysis and in vitro validation to determine the potential diagnostic and prognostic values.Methods and Results: Compared with healthy brain tissues, there was a significant increase in SYDE1 expression in glioma tissues. Additionally, SYDE1 exhibited higher expression levels in glioma patients with unfavorable clinicopathological factors. In vitro knockdown of SYDE1 in glioma cell lines A172 inhibited their migrative and invasive ability but not the proliferative ability. GO and KEGG pathway analysis of the top 100 genes coexpressed with SYDE1 showed enrichments of tumor-associated terms. Further bioinformatic analysis revealed that the SNHG16/hsa-miR-520e/SYDE1 axis might be involved in glioma development.Conclusions:SYDE1 is expressed at higher levels in gliomas than in healthy brains, and can promote metastasis and invasion but not proliferation of gliomas. Furthermore, SYDE1 has values in the diagnosis and prognosis prediction of gliomas.

A Marine λ-Oligocarrageenan Inhibits Migratory and Invasive Ability of MDA-MB-231 Human Breast Cancer Cells through Actions on Heparanase Metabolism and MMP-14/MMP-2 Axis

Sugar-based molecules such as heparins or natural heparan sulfate polysaccharides have been developed and widely studied for controlling heparanase (HPSE) enzymatic activity, a key player in extracellular matrix remodelling during cancer pathogenesis. However, non-enzymatic functions of HPSE have also been described in tumour mechanisms. Given their versatile properties, we hypothesized that sugar-based inhibitors may interfere with enzymatic but also non-enzymatic HPSE activities. In this work, we assessed the effects of an original marine λ-carrageenan derived oligosaccharide (λ-CO) we previously described, along with those of its native counterpart and heparins, on cell viability, proliferation, migration, and invasion of MDA-MB-231 breast cancer cells but also of sh-MDA-MB-231 cells, in which the expression of HPSE was selectively downregulated. We observed no cytotoxic and no anti-proliferative effects of our compounds but surprisingly λ-CO was the most efficient to reduce cell migration and invasion compared with heparins, and in a HPSE-dependent manner. We provided evidence that λ-CO tightly controlled a HPSE/MMP-14/MMP-2 axis, leading to reduced MMP-2 activity. Altogether, this study highlights λ-CO as a potent HPSE “modulator” capable of reducing not only the enzymatic activity of HPSE but also the functions controlled by the HPSE levels.

High Expression of ROMO1 Aggravates the Malignancy of Hepatoblastoma

Hepatoblastoma (HB) is a kind of tumor that occurs frequently in children and is highly malignant. Here, the function of ROS modulator 1 (ROMO1) was identified in the development of HB. In this study, the mRNA expression of ROMO1 was measured by RT-qPCR. Colony formation assay, MTT assay, and flow cytometric analysis were applied to detect cell viability. The cell migrative and invasive ability was measured by wound healing and transwell assays. Tumor xenografts were performed to examine tumor growth. The results showed that upregulation of ROMO1 was identified in liver hepatocellular carcinoma (LIHC) tissues and predicted poor prognosis in LIHC patients. And ROMO1 expression was also increased in HB tissues and cells. Functionally, ROMO1 knockdown restrained cell viability, migration, and invasion in HB. In addition, knockdown of ROMO1 was found to suppress tumor formation in vivo. In conclusion, upregulation of ROMO1 promotes tumor growth and cell aggressiveness in HB.

GATA1-induced upregulation of LINC01503 promotes carboplatin resistance in ovarian carcinoma by upregulating PD-L1 via sponging miR-766-5p

Background Ovarian Carcinoma (OCa) is a high-mortality malignancy derived from female reproductive system. Increasing evidence has identified long non-coding RNAs (lncRNAs) as important regulators in OCa chemoresistance. In this study, we intended to explore the role of LINC01503 in OCa resistance to carboplatin (CBP). Methods Gene expression was measured by reverse transcription-quantitative PCR (RT-qPCR) in OCa cells. Western blot was adopted to detect protein levels of GATA1, PD-L1, E-cadherin, N-cadherin, Vimentin, Bcl-2, Bax, cleaved caspase-3. To assess the effects of LINC01503 on the resistance of OCa cells to CBP, Cell Counting Kit-8 (CCK-8), colony formation, Transwell, and flow cytometry experiments were performed to evaluate half-maximal inhibitory concentration (IC50), cell viability, migrative and invasive ability, as well as cell apoptosis. Dual-luciferase reporter assay was employed to assess the associations between the genes. Results LINC01503 was upregulated in CBP-resistant OCa cells. LINC01503 knockdown reduced CBP resistance in OCa cells. Besides, GATA-binding protein 1 (GATA1) activated LINC01503 transcription in CBP-resistant OCa cells. MiR-766-5p was lowly expressed in CBP-resistant cells and confirmed as a target for LINC01503. In addition, miR-766-5p overexpression increased CBP sensitivity in OCa cells. PD-L1 was verified as the target of miR-766-5p. Besides, LINC01503 upregulated PD-L1 level by regulating miR-766-5p. Furthermore, rescue experiments showed that PD-L1 overexpression abrogated the inhibited impacts of blocking LINC01503 on CBP resistance in OCa cells. Conclusion GATA1-induced LINC01503 expedited CBP resistance in OCa cells via the miR-766-5p/PD-L1 axis, providing a new target for improving the efficacy of OCa chemotherapy. Graphical Abstract