ICAT-Mediated Crosstalk Between Cervical Cancer Cells and Macrophages Promotes M2-Like Macrophage Polarization to Reinforce Tumor Malignant Behaviors.

被引量：- 发表：1970

Knockdown of PAIP1 Inhibits Breast Cancer Cell Proliferation by Regulating Cyclin E2 mRNA Stability.

Polyadenylate-binding protein-interacting protein 1 (PAIP1) is a protein that modulates translation initiation in eukaryotic cells. Studies have shown that PAIP1 was overexpressed in various type of cancers, and drives cancer progression by promoting cancer cell proliferation, invasion, and migration. In our previous study, we identified that PAIP1 was overexpressed in breast cancer, and the expression was correlated with poor prognosis. However, the biological function of PAIP1 in breast cancer has not been clearly understood. In this study, we constructed PAIP1 specifically silenced breast cancer cells. Then, cell proliferation, cell cycle distribution, and apoptosis were detected in PAIP1 knockdown cells. RNA-seq analysis was performed to predict the downstream target of PAIP1, and the molecular mechanism was explored. As a results, we found that knockdown of PAIP1 repressed cell proliferation, induced cell cycle arrest, and triggers apoptosis. Xenograft mouse model showed that knockdown of PAIP1 inhibits cell growth in vivo. RNA-seq predicted that CCNE2 mRNA was one of the downstream targets of PAIP1. In addition, we identified that knockdown of PAIP1-inhibited cell proliferation through modulating cyclin E2 expression. Mechanically, knockdown of PAIP1 reduces the expression of cyclin E2 by regulating the mRNA stability of cyclin E2. Moreover, in breast cancer tissues, we found that the expression of PAIP1 was positively correlated with cyclin E2. Taken together, our findings establish the role and mechanism of PAIP1 in breast cancer progression, indicating that PAIP1 would be a new therapeutic target for breast cancer treatment.

被引量：- 发表：1970

ADAR1 Promotes Invasion and Migration and Inhibits Ferroptosis via the FAK/AKT Pathway in Colorectal Cancer.

The role of adenosine deaminase acting on RNA1 (ADAR1) in colorectal cancer (CRC) is poorly understood. This study investigated the roles and underlying molecular mechanisms of ADAR1 and its isoforms, explored the correlations between ADAR1 expression and the immune microenvironment and anticancer drug sensitivity, and examined the potential synergy of using ADAR1 expression and clinical parameters to determine the prognosis of CRC patients. CRC samples showed significant upregulation of ADAR1, and high ADAR1 expression was correlated with poor prognosis. Silencing ADAR1 inhibited the proliferation, invasion, and migration of CRC cells and induced ferroptosis by suppressing FAK/AKT activation, and the results of rescue assays were consistent with these mechanisms. Both ADAR1-p110 and ADAR1-p150 were demonstrated to regulate the FAK/AKT pathway, with ADAR1-p110 playing a particularly substantial role. In evaluating the prognosis of CRC patients, combining ADAR1 expression with clinical parameters produced a substantial synergistic effect. The in vivo tumorigenesis of CRC was significantly inhibited by silencing ADAR1. Furthermore, ADAR1 expression was positively correlated with tumor mutational burden (TMB) and microsatellite status (p < 0.05), indicating that ADAR1 plays a complex role in CRC immunotherapy. In conclusion, ADAR1 plays oncogenic roles in CRC both in vitro and in vivo, potentially by inhibiting ferroptosis via downregulation of the FAK/AKT pathway. Thus, ADAR1 serves as a potential prognostic biomarker and a promising target for CRC therapy.

被引量：- 发表：1970

Case report & review: Bilateral NIFTP harboring concomitant HRAS and KRAS mutation: Report of an unusual case and literature review.

Diagnosis and treatment of thyroid disease are affected by the wide range of thyroid cancer subtypes and their varying degrees of aggressiveness. To better describe the indolent nature of thyroid neoplasms previously classified as noninvasive follicular variant of papillary thyroid carcinoma (NI-FVPTC), the Endocrine Pathology Society working group has recently coined the term "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP). The purpose of this nomenclature change is to avoid patients the distress of cancer diagnosis and to decrease the overtreatment of thyroid nodules with a RAS-LIKE molecular profile similar to follicular adenoma. Consequently, the reclassification has a significant impact on thyroid nodule clinical care as well as histopathologic and cytopathologic diagnosis. This paper will focus on a unique case of Bilateral NIFTP harboring concomitant HRAS and KRAS mutation; we will also review the background, molecular features, and clinical implications of NIFTP as well as the factors behind the nomenclature update. It also seemed helpful to emphasize the impact of NIFTP on clinical practice to avoid overtreating nodules that could be safely managed with lobectomy alone. Actually, despite the diagnosis is postsurgery, a comprehensive preoperative evaluation may raise a suspicion of NIFTP and suggest a more careful plan for treatment. Here, we present a unique case of bilateral NIFTP after total thyroidectomy; subsequent molecular analysis revealed that the patient's right nodule harbored an isolated p.(Q61K) HRAS mutation, while the left a p.(Q61K) KRAS mutation. To the best of our knowledge, this is the first case report of this nature. The existence of simultaneous mutations highlights the occurrence of intratumoral heterogeneity (ITH) also in the context of FVPTC, which requires comprehensive investigation. The available information shows that NIFTP, identified in accordance with stringent inclusion and exclusion criteria, exhibits a very latent clinical behavior even in the face of conservative lobectomy, lacking of radioactive iodine therapy. However, it cannot be regarded as a benign lesion because there is a small but significant incidence of adverse events, such as lymph nodes and distant metastases. Currently, NIFTP can only be suspected before surgery: several efforts could be explored to identify key molecular, cytological, and ultrasonographic traits that may be helpful in raising the possibility of NIFTP in the preoperative context. Additionally, our discovery of simultaneous mutations within the same lesion strengthens the evidence of ITH even in FVPTC. Although the extent and biological impact of this phenomenon in NIFTP are still debated, a deeper understanding is essential to ensure appropriate clinical management.

被引量：- 发表：1970

Precision therapy for cancer prevention by targeting carcinogenesis.

Cancer represents a major global public health burden, with new cases estimated to increase from 14 million in 2012 to 24 million by 2035. Primary prevention is an effective strategy to reduce the costs associated with cancer burden. For example, measures to ban tobacco consumption have dramatically decreased lung cancer incidence and vaccination against human papillomavirus can prevent cervical cancer development. Unfortunately, the etiological factors of many cancer types are not completely clear or are difficult to actively control; therefore, the primary prevention of such cancers is not practical. In this review, we update the progress on precision therapy by targeting the whole carcinogenesis process, especially for three high-risk groups: (1) those with chronic inflammation, (2) those with inherited germline mutations, and (3) those with precancerous lesions like polyps, gastritis, actinic keratosis or dysplasia. We believe that attenuating chronic inflammation, treating precancerous lesions, and removing high-risk tissues harboring germline mutations are precision methods for cancer prevention.

被引量：- 发表：1970