One of the main causes of death worldwide is lung cancer, which is largely caused by cigarette smoking. The crucial transcription factor NF-κB, which controls inflammatory responses and various cellular processes, is a constitutively present cytoplasmic protein strictly regulated by inhibitors like IκB proteins. Upon activation by external stimuli, it undergoes phosphorylation, translocates into the nucleus, and modulates the expression of specific genes. The incontrovertible association between pulmonary malignancy and tobacco consumption underscores and highlights a public health concern. Polycyclic aromatic hydrocarbons and nitrosamines, potent carcinogenic compounds present in the aerosol emitted from combusted tobacco, elicit profound deleterious effects upon inhalation, resulting in severe perturbation of pulmonary tissue integrity. The pathogenesis of smoking-induced lung cancer encompasses an intricate process wherein NF-κB activation plays a pivotal role, triggered by exposure to cigarette smoke through diverse signaling pathways, including those associated with oxidative stress and pro-inflammatory cytokines. Unraveling the participation of NF-κB in smoking-induced lung cancer provides pivotal insights into molecular processes, wherein intricate crosstalk between NF-κB and pathways such as MAPK and PI3K-Akt amplifies the inflammatory response, fostering an environment conducive to the formation of lung cancer. This study reviews the critical function of NF-κB in the complex molecular pathways linked to the initiation and advancement of lung carcinogenesis as well as potential treatment targets. See also the graphical abstract(Fig. 1).

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.

Hepatocellular carcinoma (HCC) tissue is rich in dendritic cells, T cells, B cells, macrophages, natural killer cells and cellular stroma. Together they form the tumor microenvironment (TME), which is also rich in numerous cytokines. Tumor‑associated macrophages (TAMs) are involved in the regulation of tumor development. TAMs in HCC receive stimuli in different directions, polarize in different directions and release different cytokines to regulate the development of HCC. TAMs are mostly divided into two cell phenotypes: M1 and M2. M1 TAMs secrete pro‑inflammatory mediators, and M2 TAMs secrete a variety of anti‑inflammatory and pro‑tumorigenic substances. The TAM polarization in HCC tumors is M2. Both direct and indirect methods for TAMs to regulate the development of HCC are discussed. TAMs indirectly support HCC development by promoting peripheral angiogenesis and regulating the immune microenvironment of the TME. In terms of the direct regulation between TAMs and HCC cells, the present review mainly focuses on the molecular mechanism. TAMs are involved in both the proliferation and apoptosis of HCC cells to regulate the quantitative changes of HCC, and stimulate the related invasive migratory ability and cell stemness of HCC cells. The present review aims to identify immunotherapeutic options based on the mechanisms of TAMs in the TME of HCC.

Objective: To study the expressions of C-C class chemokine 17 (CCL17), C-C class chemokine 22 (CCL22), and C-C chemokine receptor 4 (CCR4) in newly diagnosed multiple myeloma (NDMM) for analyzing their correlations with clinical features and to preliminarily explore their roles in the development of NDMM. Methods: The study included 40 patients with NDMM and 20 healthy volunteers from the Department of Hematology of the Affiliated Hospital of Zunyi Medical University from July 2020 to December 2022. Peripheral blood, bone marrow, and bone marrow biopsy tissue samples were collected from the two groups. The expression levels of CCL17, CCL22, and CCR4 in patients with NDMM were analyzed using real-time quantitative reverse transcriptase polymerase chain reaction (RQ-PCR), enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry. The mRNA expression levels of CCL17, CCL22, and CCR4 in the bone marrow mononuclear cell (BMMNC) of patients with NDMM were analyzed to assess their correlations with clinical indicators. Results: The mRNA expression levels of CCL17, CCL22, and CCR4 in BMMNC were higher in patients with NDMM than in controls (all P<0.05). The protein expression levels of CCL17 and CCL22 in peripheral blood supernatants and bone marrow supernatants were higher in patients with NDMM than in controls (all P<0.05). The expression levels of CCL17, CCL22, and CCR4 in bone marrow biopsy tissues were higher in patients with NDMM than in controls (all P<0.05). The mRNA expression level of CCL17 was increased in NDMM patients with combined anemia, bone damage, renal damage, and M protein level ≥30 g/L (all P<0.05). The mRNA expression level of CCL22 was increased in NDMM patients with combined anemia, bone damage, and renal damage (all P<0.05). The mRNA expression level of CCR4 was increased in NDMM patients with combined anemia and renal damage (all P<0.05) . Conclusion: CCL17, CCL22, and CCR4 were highly expressed in clinical samples from patients with NDMM compared to those from controls, and they may be involved in the occurrence and development of NDMM.
目的： 研究CCL17、CCL22及CCR4在新诊断多发性骨髓瘤（NDMM）中的表达情况，分析其与临床特征的相关性，初步探讨其在NDMM发生发展中的作用。 方法： 选取2020年7月至2022年12月在遵义医科大学附属医院血液内科就诊的40例NDMM患者以及20名健康志愿者作为研究对象，收集两组外周血、骨髓及骨髓活检组织样本并通过RQ-PCR、ELISA、免疫组化检测NDMM患者的CCL17、CCL22以及CCR4的表达水平。分析NDMM患者骨髓单个核细胞（BMMNC）中CCL17、CCL22及CCR4的mRNA表达水平与患者临床指标的相关性。 结果： NDMM患者BMMNC中CCL17、CCL22及CCR4的mRNA表达水平均高于健康志愿者（对照组）（P值均<0.001）；NDMM患者外周血上清和骨髓上清中CCL17、CCL22的蛋白表达水平均高于对照组（P值均<0.001）；NDMM患者骨髓活检组织中CCL17、CCL22及CCR4的表达水平均高于对照组（P值均<0.05）。CCL17 mRNA在合并贫血、骨质损害、肾损害以及单克隆免疫球蛋白≥30 g/L的NDMM患者中表达水平上升（P值均<0.05）；CCL22 mRNA在合并贫血、骨质损害、肾损害的NDMM患者中表达水平上升（P值均<0.05）；CCR4 mRNA在合并贫血、肾损害的NDMM患者中表达水平上升（P值均<0.05）。 结论： 与对照组相比，CCL17、CCL22及CCR4在NDMM患者临床样本中均呈高表达，可能参与了NDMM的发生及发展。.

Breast cancer, a pervasive and complex disease, continues to pose significant challenges in the field of oncology. Its heterogeneous nature and diverse molecular profiles necessitate a nuanced understanding of the underlying mechanisms driving tumorigenesis and progression. MicroRNA-21 (miR-21) has emerged as a crucial player in breast cancer development and progression by modulating apoptosis, a programmed cell death mechanism that eliminates aberrant cells. MiR-21 overexpression is a hallmark of breast cancer, and it is associated with poor prognosis and resistance to conventional therapies. This miRNA exerts its oncogenic effects by targeting various pro-apoptotic genes, including Fas ligand (FasL), programmed cell death protein 4 (PDCD4), and phosphatase and tensin homolog (PTEN). By suppressing these genes, miR-21 promotes breast cancer cell survival, proliferation, invasion, and metastasis. The identification of miR-21 as a critical regulator of apoptosis in breast cancer has opened new avenues for therapeutic intervention. This review investigates the intricate mechanisms through which miR-21 influences apoptosis, offering insights into the molecular pathways and signaling cascades involved. The dysregulation of apoptosis is a hallmark of cancer, and understanding the role of miR-21 in this context holds immense therapeutic potential. Additionally, the review highlights the clinical significance of miR-21 as a diagnostic and prognostic biomarker in breast cancer, underscoring its potential as a therapeutic target.

EIF1AX mutation has been identified as a driver mutation for papillary thyroid carcinoma (PTC) by The Cancer Genome Atlas (TCGA) study. Subsequent studies confirmed this mutation in PTC and Anaplastic Thyroid Carcinoma (ATC) but also reported EIF1AX mutation in Follicular nodular disease (FND) and benign thyroid nodules. In this study, we review thyroid nodules with EIF1AX mutation from two institutions: a tertiary care hospital (YNHH, n = 22) and a major cancer referral center (MSKCC, n = 34) and report the varying histomorphology in the context of additional genetic abnormalities and institutional practices. Pathology diagnoses were reviewed according to the WHO 5th edition and correlated with the type of EIF1AX mutation and additional concurrent molecular alterations, if any. Most cases were splice site type mutations. Cases consisted of 9 FND, 7 follicular (FA) or oncocytic adenomas (OA), 2 non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) and 38 follicular-cell derived thyroid carcinomas. Of 8 cases with isolated EIF1AX mutation, 7 were FND, FA or OA (88%) and one was an oncocytic carcinoma (12%). Of 12 cases with EIF1AX and one additional molecular alteration, 9 (75%) were FND, FA or OA, 2 (17%) were NIFTPs and one (8%) was a poorly differentiated thyroid carcinoma. All 36 cases with EIF1AX mutation and ≥ 2 molecular alterations were malignant (100%) and included TP53 and TERT promoter mutations associated with ATC (n = 8) and high-grade follicular cell-derived non-anaplastic carcinoma (HGC, n = 2). Isolated EIF1AX mutation was noted only in thyroid nodules seen at YNHH and were predominantly encountered in benign thyroid nodules including FND. Accumulation of additional genetic abnormalities appears to be progressively associated with malignant tumors.

Mucinous cystic neoplasm (MCN) is one of the precursor lesions of pancreatic ductal adenocarcinoma and intrahepatic cholangiocarcinoma. The aim of this study is to examine the presence of short telomeres in promoting the tumorigenesis of MCN by measuring telomere lengths in distinct components of MCN, including the mucinous lining epithelium, non-mucinous lining epithelium, and ovarian-type stroma. A total of 45 patients with MCN (30 pancreatic and 15 hepatic cases) were obtained. Quantitative telomere-specific fluorescent in situ hybridization was performed to measure the telomere length of specific cell types within MCNs, including mucinous lining epithelium, non-mucinous lining epithelium, and ovarian-type stroma, as well as normal ductal epithelium and adenocarcinoma. Relative telomere lengths tended to decrease between normal ductal epithelium, ovarian-type stroma, non-mucinous lining epithelium, mucinous lining epithelium, and adenocarcinoma regardless of the involved organs. Among the analyzed cell types, relative telomere lengths were significantly different between normal ductal epithelium (3.31 ± 0.78), ovarian-type stroma (2.90 ± 0.93), non-mucinous lining epithelium (2.84 ± 0.79), mucinous lining epithelium (2.49 ± 0.93), and adenocarcinoma (1.19 ± 0.59), respectively (P < 0.001, mixed-effects model). As expected, no difference in relative telomere lengths was observed between normal ductal epithelium and ovarian-type stroma; however, significant differences were observed in pair-wise comparisons between ovarian-type stroma vs. non-mucinous lining epithelium (P = 0.001), non-mucinous lining epithelium vs. mucinous lining epithelium (P = 0.005), and mucinous lining epithelium vs. adenocarcinoma (P < 0.001). These findings suggest gradual telomere shortening occurs in the tumorigenesis of MCN, which may have important implications for the progression of this disease.

Liver cancer is one of the most lethal gastrointestinal malignancies. Emerging evidence has underscored the pivotal role of long non-coding RNAs (lncRNAs) in tumorigenesis, with ST8SIA6-AS1 identified as a novel oncogenic lncRNA contributing to liver cancer progression. ST8SIA6-AS1 is consistently upregulated in hepatic cancer tissues and is strongly associated with unfavorable prognosis. Moreover, it demonstrates high diagnostic efficacy in detecting HCC. ST8SIA6-AS1 is involved in various cellular processes including proliferation, migration, and invasion, primarily through its function as a competing endogenous RNA (ceRNA), thereby facilitating hepatocarcinogenesis and disease advancement. This review provides a detailed examination of the molecular functions and regulatory mechanisms of ST8SIA6-AS1 in hepatocellular carcinoma (HCC) and highlights its potential as a promising biomarker for liver cancer, aiming to propel the development of innovative therapeutic strategies for HCC management.

SOluble Resistance-related Calcium-binding proteIN (sorcin) earned its name due to its co-amplification with ABCB1 in multidrug-resistant cells. Initially thought to be an accidental consequence of this co-amplification, recent research indicates that sorcin plays a more active role as an oncoprotein, significantly impacting multidrug resistance (MDR). Sorcin is a highly expressed calcium-binding protein, often overproduced in human tumors and multidrug-resistant cancers, and is a promising novel MDR marker. In tumors, sorcin levels inversely correlate with both patient response to chemotherapy and overall prognosis. Multidrug-resistant cell lines consistently exhibit higher sorcin expression compared to their parental counterparts. Furthermore, sorcin overexpression via gene transfection enhances drug resistance to various chemotherapeutic drugs across numerous cancer lines. Conversely, silencing sorcin expression reverses drug resistance in many cell lines. Sorcin participates in several mechanisms of MDR, including drug efflux, drug sequestering, cell death inhibition, gene amplification, epithelial-to-mesenchymal transition, angiogenesis, and metastasis. The present review focuses on the structure and function of sorcin, on sorcin\'s role in cancer and drug resistance, and on the approaches aimed at targeting sorcin.

N6-methyladenosine (m6A) represents the most prevalent and significant internal modification in mRNA, with its critical role in gene expression regulation and cell fate determination increasingly recognized in recent research. The immune system, essential for defense against infections and maintaining internal stability through interactions with other bodily systems, is significantly influenced by m6A modification. This modification acts as a key post-transcriptional regulator of immune responses, though its effects on different immune cells vary across diseases. This review delineates the impact of m6A modification across major system-related cancers-including those of the respiratory, digestive, endocrine, nervous, urinary reproductive, musculoskeletal system malignancies, as well as acute myeloid leukemia and autoimmune diseases. We explore the pathogenic roles of m6A RNA modifications within the tumor immune microenvironment and the broader immune system, highlighting how RNA modification regulators interact with immune pathways during disease progression. Furthermore, we discuss how the expression patterns of these regulators can influence disease susceptibility to immunotherapy, facilitating the development of diagnostic and prognostic models and pioneering new therapeutic approaches. Overall, this review emphasizes the challenges and prospective directions of m6A-related immune regulation in various systemic diseases throughout the body.