circNDUFB2 inhibits non-small cell lung cancer progression via destabilizing IGF2BPs and activating anti-tumor immunity
Botai LiLili ZhuChunlai LuCun WangHui WangHaojie JinXuhui MaZhuoan ChengChengtao YuSiying WangQiaozhu ZuoYangyang ZhouJun WangChen YangYuanyuan LvLiyan JiangWenxin Qin
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Abstract Circular RNAs (circRNA) are a class of covalently closed single-stranded RNAs that have been implicated in cancer progression. Here we identify circNDUFB2 to be downregulated in non-small cell lung cancer (NSCLC) tissues, and to negatively correlate with NSCLC malignant features. Elevated circNDUFB2 inhibits growth and metastasis of NSCLC cells. Mechanistically, circNDUFB2 functions as a scaffold to enhance the interaction between TRIM25 and IGF2BPs, a positive regulator of tumor progression and metastasis. This TRIM25/circNDUFB2/IGF2BPs ternary complex facilitates ubiquitination and degradation of IGF2BPs, with this effect enhanced by N 6 -methyladenosine (m 6 A) modification of circNDUFB2 . Moreover, circNDUFB2 is also recognized by RIG-I to activate RIG-I-MAVS signaling cascades and recruit immune cells into the tumor microenvironment (TME). Our data thus provide evidences that circNDUFB2 participates in the degradation of IGF2BPs and activation of anti-tumor immunity during NSCLC progression via the modulation of both protein ubiquitination and degradation, as well as cellular immune responses.Keywords:
Tumor progression
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The tumor microenvironment has been widely implicated in tumorigenesis because it harbors tumor cells that interact with surrounding cells through the circulatory and lymphatic systems to influence the development and progression of cancer. In addition, nonmalignant cells in the tumor microenvironment play critical roles in all the stages of carcinogenesis by stimulating and facilitating uncontrolled cell proliferation.This study aims to explore the concept of the tumor microenvironment by conducting a critical review of previous studies on the topic. Materials and Methods: This review relies on evidence presented in previous studies related to the topic. The articles included in this review were obtained from different medical and health databases.The tumor microenvironment has received significant attention in the cancer literature, with a particular focus on its role in tumor development and progression. Previous studies have identified various components of the tumor microenvironment that influence malignant behavior and progression. In addition to malignant cells, adipocytes, fibroblasts, tumor vasculature, lymphocytes, dendritic cells, and cancer-associated fibroblasts are present in the tumor microenvironment. Each of these cell types has unique immunological capabilities that determine whether the tumor will survive and affect neighboring cells.The tumor microenvironment harbors cancer stem cells and other molecules that contribute to tumor development and progression. Consequently, targeting and manipulating the cells and factors in the tumor microenvironment during cancer treatment can help control malignancies and achieve positive health outcomes.
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Thermal ablation (TA), including radiofrequency ablation (RFA) and microwave ablation (MWA), has become the main treatment for early-stage hepatocellular carcinoma (HCC) due to advantages such as safety and minimal invasiveness. However, HCC is prone to local recurrence, with more aggressive malignancies after TA closely related to TA-induced changes in epithelial-mesenchymal transition (EMT) and remodeling of the tumor microenvironment (TME). According to many studies, various components of the TME undergo complex changes after TA, such as the recruitment of innate and adaptive immune cells, the release of tumor-associated antigens (TAAs) and various cytokines, the formation of a hypoxic microenvironment, and tumor angiogenesis. Changes in the TME after TA can partly enhance the anti-tumor immune response; however, this response is weak to kill the tumor completely. Certain components of the TME can induce an immunosuppressive microenvironment through complex interactions, leading to tumor recurrence and progression. How the TME is remodeled after TA and the mechanism by which the TME promotes HCC recurrence and progression are unclear. Thus, in this review, we focused on these issues to highlight potentially effective strategies for reducing and preventing the recurrence and progression of HCC after TA.
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Abstract Although it is well recognized that the tumor microenvironment plays a key role in regulating tumor progression, the mechanisms through which this occurs need to be defined. Current international research activities toward defining the role of the tumor microenvironment in cancer progression were the subject of the first Tianjin Forum on Tumor Microenvironment held at Nankai University in Tianjin, China, July 2 to 4, 2010. The importance of variety of processes, such as inflammation and angiogenesis, in the role of tumor progression was described for multiple tumor types including breast, prostate, and hepatic cancers, as well as the process of bone metastasis. Identification of novel signaling pathways that impact both angiogenesis and bone remodeling were presented. Several themes emerged from this meeting, such as: (i) tumor cells modify the microenvironment to enhance their own survival and progression; (ii) targeting host factors, in addition to targeting tumor cells, will have important therapeutic effects; and (iii) host cells distribution within the tumor has both prognostic and therapeutic significance. Several priorities for future research were defined including use of a systems biology approach to define the role of host factors in tumor progression, to define the importance of targeting both arms of the bone remodeling process for therapy of bone metastasis, and to determine how different cell subsets contribute to microenvironment-mediated regulation of tumor progression. Cancer Res; 71(2); 310–3. ©2011 AACR.
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Distinct tumor microenvironment forms in each progression step of cancer and has diverse capacities to induce both adverse and beneficial consequences for tumorigenesis. It is now known that immune cells can be activated to favor tumor growth and progression, most probably influenced by the tumor microenvironment. Tumor-associated macrophages and tumor-associated neutrophils can exert protumoral functions, enhancing tumor cell invasion and metastasis, angiogenesis, and extracellular matrix remodeling, while inhibiting the antitumoral immune surveillance. Considering that neutrophils in inflammatory environments recruit macrophages and that recruited macrophages affect neutrophil functions, there may be various degrees of interaction between tumor-associated macrophages and tumor-associated neutrophils. Platelets also play an important role in the recruitment and regulation of monocytic and granulocytic cells in the tumor tissues, suggesting that platelet function may be essential for generation of tumor-associated macrophages and tumor-associated neutrophils. In this review, we will explore the biology of tumor-associated macrophages and tumor-associated neutrophils and their possible interactions in the tumor microenvironment. Special attention will be given to the recruitment and activation of these tumor-associated cells and to the roles they play in maintenance of the tumor microenvironment and progression of tumors.
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<div>Abstract<p>Although it is well recognized that the tumor microenvironment plays a key role in regulating tumor progression, the mechanisms through which this occurs need to be defined. Current international research activities toward defining the role of the tumor microenvironment in cancer progression were the subject of the first Tianjin Forum on Tumor Microenvironment held at Nankai University in Tianjin, China, July 2 to 4, 2010. The importance of variety of processes, such as inflammation and angiogenesis, in the role of tumor progression was described for multiple tumor types including breast, prostate, and hepatic cancers, as well as the process of bone metastasis. Identification of novel signaling pathways that impact both angiogenesis and bone remodeling were presented. Several themes emerged from this meeting, such as: (i) tumor cells modify the microenvironment to enhance their own survival and progression; (ii) targeting host factors, in addition to targeting tumor cells, will have important therapeutic effects; and (iii) host cells distribution within the tumor has both prognostic and therapeutic significance. Several priorities for future research were defined including use of a systems biology approach to define the role of host factors in tumor progression, to define the importance of targeting both arms of the bone remodeling process for therapy of bone metastasis, and to determine how different cell subsets contribute to microenvironment-mediated regulation of tumor progression. <i>Cancer Res; 71(2); 310–3. ©2011 AACR</i>.</p></div>
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