Research Progress of Axl Inhibitors

2019 ◽  
Vol 19 (15) ◽  
pp. 1338-1349 ◽  
Author(s):  
Zhi-Gang Sun ◽  
Jian-Hua Liu ◽  
Jin-Mai Zhang ◽  
Yong Qian
Keyword(s):  
Skeletal Muscle ◽  
Signal Transduction ◽  
Cell Proliferation ◽  
Drug Resistance ◽  
Receptor Tyrosine Kinase ◽  
Chemotherapy Resistance ◽  
Research Progress ◽  
Invasion And Metastasis ◽  
Over Expression ◽  
Pancreatic Cancers

Axl, a Receptor Tyrosine Kinase (RTK) belonging to the TAM (Axl, Mer, Tyro3) family, participates in many signal transduction cascades after mostly being stimulated by Growth arrestspecific 6(Gas6). Axl is widely expressed in many organs, such as macrophages, endothelial cells, heart, liver and skeletal muscle. Over-expression and activation of Axl are associated with promoting chemotherapy resistance, cell proliferation, invasion and metastasis in many human cancers, such as breast, lung, and pancreatic cancers. Therefore, the research and development of Axl inhibitors is of great significance to strengthen the means of cancer treatment, especially to solve the problem of drug resistance. Axl inhibitors have attracted more and more researchers' attention in recent years. This review discusses the research progress of Axl inhibitors in recent years.

Oncogenic LncRNA CASC9 in Cancer Progression

2020 ◽  
Vol 26 ◽  
Author(s):  
Yuying Qi ◽  
Chaoying Song ◽  
Jiali Zhang ◽  
Chong Guo ◽  
Chengfu Yuan
Keyword(s):  
Cell Proliferation ◽  
Drug Resistance ◽  
Cell Growth ◽  
Cancer Cells ◽  
Therapeutic Potential ◽  
Squamous Metaplasia ◽  
Neoplastic Transformation ◽  
Over Expression ◽  
Human Cancers ◽  
Current Review

Background: Long non-coding RNA (LncRNAs), with the length over 200 nucleotides, originate from intergenic, antisense, or promoter-proximal regions, is a large family of RNAs that lack coding capacity. Emerging evidences illustrated that LncRNAs played significant roles in a variety of cellular functions and biological processes in profuse human diseases, especially in cancers. Cancer susceptibility candidate 9 (CASC9), as a member of the LncRNAs group, was firstly found its oncogenic function in esophageal cancer. In following recent studies, a growing amount of human malignancies are verified to be correlated with CASC9, most of which are derived from the squamous epithelium tissue. This present review attempts to highlight the latest insights into the expression, functional roles, and molecular mechanisms of CASC9 in different human malignancies. Methods: In this review, the latest findings related to the pathophysiological processes of CASC9 in human cancers were summarized and analyzed, the associated studies were collected in systematically retrieval of PubMed used lncRNA and CASA9 as keywords. Results: CASC9 expression is identified to be aberrantly elevated in a variety of malignancies. The over-expression of CASC9 has been suggested to accelerate cell proliferation, migration, cell growth and drug resistance of cancer cells, while depress cell apoptosis, revealing its role as an oncogene. Moreover, the current review demonstrated CASC9 closely relates to neoplastic transformation of squamous epithelial cells and squamous metaplasia in non-squamous epithelial tissues. Finally, we discuss the limitations and tremendous diagnostic/therapeutic potential of CASC9 in various human cancers. Results: CASC9 expression is identified to be aberrantly elevated in a variety of malignancies. The over-expression of CASC9 has been suggested to accelerate cell proliferation, migration, cell growth and drug resistance of cancer cells, while depress cell apoptosis, revealing its role as an oncogene. Moreover, the current review demonstrated CASC9 closely relates to neoplastic transformation of squamous epithelial cells and squamous metaplasia in non-squamous epithelial tissues. Finally, we discuss the limitations and tremendous diagnostic/therapeutic potential of CASC9 in various human cancers. Conclusion: Long non-coding RNACASC9 likely served as useful disease biomarkers or therapy targets that could effectively apply in treatment of different kinds of cancers.

scholarly journals Current Research Progress on Long Noncoding RNAs Associated with Hepatocellular Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Haihong Shi ◽  
Yuxin Xu ◽  
Xin Yi ◽  
Dandan Fang ◽  
Xia Hou
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Liver Cancer ◽  
Biological Activities ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Research Progress ◽  
Invasion And Metastasis ◽  
Complex Processes ◽  
And Function

Hepatocellular carcinoma (HCC) is the second leading cause of mortality among cancers. It has been found that long noncoding RNAs (lncRNAs) are involved in many human cancers, including liver cancer. It has been identified that carcinogenic and tumor-suppressing lncRNAs are associated with complex processes in liver cancer. These lncRNAs may participate in a variety of pathological and biological activities, such as cell proliferation, apoptosis, invasion, and metastasis. Here, we review the regulation and function of lncRNA in liver cancer and evaluate the potential of lncRNA as a new goal for liver cancer.

Mechanism of long-chain non-coding RNA hypoxia-inducible factor 1α-antisense RNA 1 regulating chemotherapy resistance of retinoblastoma by inhibiting hypoxia-inducible factor-α expression

2021 ◽  
Vol 11 (11) ◽  
pp. 1874-1880
Author(s):  
Cao Gu ◽  
Qing Li ◽  
Shaofei Zhao ◽  
Yu Gao ◽  
Peirong Lu
Keyword(s):  
Cell Proliferation ◽  
Drug Resistance ◽  
Cell Survival ◽  
Treatment Effectiveness ◽  
Hypoxia Inducible Factor ◽  
Chemotherapy Resistance ◽  
Non Coding Rna ◽  
Reduce Cell Proliferation ◽  
Factor Α ◽  
Infants And Young Children

Retinoblastoma (Rb) mostly occurs in infants and young children with weak resistance. Surgical treatment causes great damage to children’s appearance, so adjuvant chemotherapy is needed to reduce the damage. But chemotherapeutic resistance affects treatment effectiveness and may even lead to the death of the child. Exploring the specific mechanism of drug resistance in Rb children is helpful to improve the therapeutic effect. It was found that the relative expression in Rb cell Y79, SO-Rb50, and HXO-Rb44 was greatly higher than that in normal hum an retinal cells. After transfection of SI-HIF1A-AS1 into Rb cells, the expression of lncRNA HIF1A-AS1 was decreased greatly, and the level of HIF-1α was down-regulated. Suppress lncRNA HIF1A-AS1 expression can reduce cell proliferation and improve apoptosis. Based on the overexpression of HIF-1α, the cell proliferation ability was restored partially, and the apoptosis ability was reduced greatly. When cells were cultured with vincristine, we found that suppress lncRNA HIF1A-AS1 expression can decrease cell survival, and overexpression of HIF-1α improved cell survival. The above results confirmed that inhibition of lncRNA HIF1AAS1 expression could reduce drug resistance of Y97 cells, while overexpression of HIF-1α can antagonize the drug resistance of low expression lncRNA HIF1A-AS1 against Rb cells. Therefore, this study suggests that lncRNA HIF1A-AS1 may regulate Rb cells’ resistance to vincristine by regulating HIF-1α expression.

scholarly journals Research Progress of MicroRNA in Chemotherapy Resistance of Osteosarcoma

2021 ◽  
Vol 20 ◽  
pp. 153303382110342
Author(s):  
Zhaopeng Tang ◽  
Yubao Lu ◽  
Yutong Chen ◽  
Jiarui Zhang ◽  
Zhijun Chen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Effective Treatment ◽  
Cancer Cells ◽  
Metabolic Response ◽  
Chemotherapy Resistance ◽  
Chemotherapeutic Agents ◽  
Medical Community ◽  
Research Progress ◽  
Community Studies ◽  
Chemotherapy Drugs

Osteosarcoma (OS) is a malignant tumor prevalent in adolescents; however, a clinically effective treatment for this malignancy is lacking. The lack of effective treatment methods and factors, such as recurrence and drug resistance, further dampen the prospect of clinically treating OS. In recent years, small molecule microRNAs (miRNAs) with a length of approximately 20-24 nucleotides have gradually attracted the attention of the medical community. Studies have found that miRNAs can regulate the cell cycle, apoptosis, cell proliferation, and cell proliferation. The metabolic response of cancer cells, invasion and metastasis of cancer cells, and angiogenesis play an important role in the process of tumorigenesis. miRNAs regulate gene expression by regulating mRNA expression after transcription. A large amount of data from many studies indicate that they have diagnostic and prognostic biomarker effects in OS and are involved in regulating the metabolism of cancer cells and resistance or sensitivity to chemotherapy drugs. Chemotherapy resistance is one of the most critical problems in clinically treating OS. A large number of basic studies and systematic summaries are required to provide a theoretical basis for elucidating the mechanism and drug development of chemotherapeutic agents. Therefore, this article discusses the role of miRNAs in OS resistance. Herein, the related research progress of the studies is reviewed to provide more useful information for the development of effective therapy.

scholarly journals Inhibition of Kelch-like epichlorohydrin-related protein 1 promotes the progression and drug resistance of lung adenocarcinoma

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11908
Author(s):  
Hong Gao ◽  
Peipei Tang ◽  
Kejie Ni ◽  
Lun Zhu ◽  
Song Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Drug Resistance ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Lung Adenocarcinoma ◽  
Chemotherapy Resistance ◽  
Related Protein ◽  
H1299 Cell ◽  
Node Metastasis

Background Lung cancer is a common malignant carcinoma of respiratory system with high morbidity and mortality. Kelch-like epichlorohydrin-related protein 1 (Keap1), a member of the BTB-Kelch protein family, has been reported as an important molecule in several cancers. However, its potential role in tumor is still controversial. Here we aim to clarify the effect of Keap1 on the biological characteristics and chemotherapy resistance in lung adenocarcinoma (LUAD). Methods Immunohistochemistry was conducted to compare Keap1 expression in lung adenocarcinoma tissues and matched non-cancerous tissues, and the correlation between Keap1 expression and clinicopathological features was analyzed. Subsequently, the stable A549 and H1299 cell lines with Keap1 knockdown or overexpression were constructed using lentivirus. The roles of Keap1 on the cell proliferation, migration, invasion and drug resistance were investigated by colony formation assay, cell proliferation assay, wound scratch test, transwell invasion assay and drug sensitivity assay, respectively. Results Keap1 was lowly expressed in tumor tissues compared to matched non-cancerous tissues, and its expression was correlated with TNM stage and lymph node metastasis. Early stage (I) tumors without lymph node metastasis had higher levels of Keap1 expression compared with late-stage tumors (II, III) with the presence of lymphatic metastasis. Colony formation assays showed that Keap1 knockdown promoted the proliferation of A549 and H1299 cells, and the cell growth curves further confirmed this feature. In contrast, wound scratch and transwell invasion experiments showed that Keap1 overexpression inhibited cell migration and invasive malignancy. The IC50 for cisplatin and paclitaxel were significantly increased by Keap1 knockdown in A549 and H1299 cell lines. Conclusion Keap1 knockdown promotes tumor cell growth, proliferation, invasion, metastasis and chemotherapy resistance in LUAD. It may be a potential tumor marker to guide the staging and treatment of lung cancer.

scholarly journals HAX1 Augments Cell Proliferation, Migration, Adhesion, and Invasion Induced by Urokinase-Type Plasminogen Activator Receptor

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Ahmed H. Mekkawy ◽  
David L. Morris ◽  
Mohammad H. Pourgholami
Keyword(s):  
Signal Transduction ◽  
Cell Proliferation ◽  
Plasminogen Activator ◽  
Physiological Role ◽  
Cell Surface Receptor ◽  
Migration And Invasion ◽  
Over Expression ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Plasminogen Activator Receptor

The urokinase-type plasminogen activator receptor (uPAR) is a cell surface receptor which has a multifunctional task in the process of tumorigenesis including cell proliferation, adhesion, migration, and invasion. Many of the biological functions of uPAR necessitate interactions with other proteins. We have shown previously that uPAR interacts with HAX1 protein (HS-1-associated protein X-1). In the current study, to gain insight into the possible role of HAX1 overexpression in regulation of uPAR signal transduction pathway, several function assays were used. We found that, upon stimulation of uPAR, HAX1 colocalizes with uPAR suggesting a physiological role for HAX1 in the regulation of uPAR signal transduction. HAX1 overexpression augments cell proliferation and migration in uPAR-stimulated cells. Moreover, HAX1 over-expression augmented uPAR-induced cell adhesion to vitronectin as well as cellular invasion. Our results suggest that HAX1 over-expression may underlay a novel mechanism to regulate uPAR-induced functions in cancer cells.

scholarly journals Decreased Expression of Nucleophosmin/B23 Increases Drug Sensitivity of Adriamycin-Resistant Lymphoblastic Leukemia Molt-4 Cells through mdr-1 Regulation

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5229-5229
Author(s):  
Jianda Hu ◽  
Lingyan Wang ◽  
Buyuan Chen ◽  
MinHui Lin ◽  
Yanqin Cao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Drug Resistance ◽  
Drug Sensitivity ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Aberrant Expression ◽  
Poor Prognostic Factor ◽  
Over Expression ◽  
Response To Chemotherapy ◽  
Mdr 1

Abstract Nucleophosmin /B23 (NPM, also known as B23, numatrin, or N038) is regularly identified as multifunctional nuclear protein, not only an important player in ribosome biogenesis but also a potential regulator for cell proliferation. Aberrant expression of NPM, such as mutation, deletion, over-expression or rearrangement, could lead to malignant transformation in tumor cells. It is reported that over-expression of NPM in solid tumor had been detected as a poor prognostic factor and related to drug-resistance development. In adult de novo acute myeloid leukemia (AML), mutated NPM without FLT3-ITD showed a good response to chemotherapy in AML. Although a great deal of knowledge of NPM has been accumulated, little information on the role of NPM in drug resistance in leukemia is available. According to our previous investigation, NPM levels are up regulated in drug-resistant cell lines and primary leukemic cells. High expressions of NPM could be observed in refractory or relapsed acute leukemia patients, which significantly correlated with poor prognosis. In this study, we wanted to evaluate whether NPM is involved in drug resistance in lymphocytic leukemia cells. We generated an adriamycin (ADM)-resistant lymphoblastic cell line Molt-4/ADR (MAR). Cell proliferation, sensitivity to chemotherapy agents and expressions of drug resistance related molecules were assessed. The IC50 of Molt-4 cells were 0.584±0.113umol/L and of MAR cells were 22.56±1.94 umol/L, meaning MAR cells were 38.63 fold resistant to ADM. The confocal microscopy assay showed that MAR cells had very low levels of ADM fluorescence, however, when treated with the P-gp inhibitor Verapamil Hydrochloride, ADM accumulation in MAR cells increased greatly. These cells were not only resistant to other MDR agents like daunorubicin and vincristine, but also slightly resistant to a panel of non-MDR agents, such as VP-16 and cyclophosphamide. Furthermore, MAR cells gained an expression of mdr-1(P-gp) and a higher expression of NPM compared to Molt-4 cells. Knockdown of NPM by RNA interference (RNAi) suppressed the viability of both Molt-4 and MAR cells. In both Molt-4 and MAR cells, IC 50 of NPM knockdown groups decreased sharply. IC50 of Molt-4 cells was reduced from 0.582±0.112 μmol/L before NPM RNAi to 0.186±0.019μmol/L after NPM RNAi. IC50 of MAR was reduced from 22.56±1.94μmol/L before NPM RNAi to 3.83±0.381μmol/L after NPM RNAi. Knocking down NPM not only increased Molt-4 cells’ drug sensitivity but also reverse resistance of MAR towards Adriamycin. With an increase of drug sensitivity, we found the down-regulation of P-gp and Akt /mTOR signaling in MAR cells after NPM RNAi. To further understanding the relationship between NPM and mdr-1, we applied RNAi to down-regulate mdr-1 in MAR cells. Knockdown of mdr-1 could also reverse the drug resistance. NPM expression revealed no significantly fluctuation after mdr-1 silencing . It could be concluded that knockdown of NPM reversed the drug resistance by down-regulating P-gp and Akt /mTOR signal pathway, indicating that NPM may serve as a potential modulator in drug resistance. Disclosures No relevant conflicts of interest to declare.

scholarly journals The Role of RNA Methyltransferase METTL3 in Hepatocellular Carcinoma: Results and Perspectives

2021 ◽  
Vol 9 ◽  
Author(s):  
Fan Pan ◽  
Xin-Rong Lin ◽  
Li-Ping Hao ◽  
Xiao-Yuan Chu ◽  
Hai-Jun Wan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Drug Resistance ◽  
Rna Splicing ◽  
Tumor Invasion ◽  
Rapid Development ◽  
Rna Expression ◽  
Dependent Manner ◽  
Invasion And Metastasis

Hepatocellular carcinoma (HCC) is the 6th most prevalent cancer and the 4th leading cause of cancer-related death worldwide. Mechanisms explaining the carcinogenesis of HCC are not clear yet. In recent years, rapid development of N6-methyladenosine (m6A) modification provides a fresh approach to disclosing this mystery. As the most prevalent mRNA modification in eukaryotes, m6A modification is capable to post-transcriptionally affect RNA splicing, stability, and translation, thus participating in a variety of biological and pathological processes including cell proliferation, apoptosis, tumor invasion and metastasis. METTL3 has been recognized as a pivotal methyltransferase and essential to the performance of m6A modification. METTL3 can regulate RNA expression in a m6A-dependent manner and contribute to the carcinogenesis, tumor progression, and drug resistance of HCC. In the present review, we are going to make a clear summary of the known roles of METTL3 in HCC, and explicitly narrate the potential mechanisms for these roles.

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