Chunlin Ou

P‑element induced wimpy testis (PIWI)‑interacting RNAs (piRNAs) are small non‑coding RNAs with a length of ~24‑32 nucleotides that specifically bind members of the PIWI protein family. Initially identified in germ cells, piRNAs have since been detected in various somatic cells. They regulate multiple physiological and pathological processes and their aberrant expression contributes to human diseases, including cancer. Recent studies indicate that piRNAs influence key tumour behaviours‑including malignant proliferation, invasion and metastasis, angiogenesis, immune evasion and metabolic reprogramming‑through epigenetic, transcriptional and post‑transcriptional mechanisms. In tumour‑bearing mouse models, exogenous knockdown or overexpression of piRNAs using nanodelivery systems can markedly inhibit tumour growth, supporting their potential as therapeutic targets. piRNAs are also stably expressed in tumour tissues and bodily fluids, such as serum and urine, either freely circulating or encapsulated within extracellular vesicles; their dysregulation is associated with clinicopathological features of tumours. Accordingly, piRNAs may serve as novel pathological diagnostic markers or liquid biopsy biomarkers. This review summarises piRNA expression patterns and molecular mechanisms, evaluates their clinical potential in cancer diagnosis and treatment and integrates advances in high‑throughput sequencing and nanodelivery technologies to provide a theoretical basis and research foundation for the clinical translation of piRNA‑related studies.

Complexity of the microenvironment of lung adenocarcinoma (LUAD) poses significant challenges in its clinical management. Systematic bioinformatic analysis of the Ras-association domain family (RASSF) identified RASSF2 as a potential tumour suppressor in LUAD. This study aims to investigate its clinical significance and functional mechanisms in LUAD. CCK-8, EdU, and colony formation assays were performed to investigate the impact of RASSF2 overexpression on the proliferative capacity of LUAD cells. Transwell and wound healing assays were performed to explore the significance of RASSF2 on LUAD cell migration and invasion. RNA sequencing analysis was conducted on three methylation-positive and three methylation-negative LUAD tissue samples to establish the underlying mechanism of RASSF2 methylation in LUAD. Functional studies indicated that RASSF2 overexpression significantly inhibited the proliferation, migration, and invasion of LUAD cells. Patients with RASSF2 promoter hypermethylation exhibited a significantly shorter overall survival than those without. RNA-seq of three pairs of LUAD tissue samples further demonstrated that RASSF2 methylation is associated with upregulation of the NF-κB signalling pathway and dysregulation of T-cell activation pathways. This study confirmed the tumour-suppressive role of RASSF2 in LUAD and suggests its potential as an immunotherapeutic target, thus providing new insights into LUAD treatment strategies.

Angiotensin-converting enzyme 2 (ACE2) has been implicated as an oncogene in certain cancer types; however, there is a lack of analysis on the role of ACE2 in the predictive value for prognosis and immunotherapy response in various tumor types. This study used data from the Cancer Genome Atlas (TCGA), Tumor Immune Estimation Resource (TIMER 2.0), cBioPortal, and ROC Plotter databases to analyze the expression, prognosis, and immune cell infiltration of ACE2 in various tumor types. Furthermore, we analyzed the correlation between the expression of ACE2 and clinicopathological characteristics in 119 pairs of colorectal cancer (CRC) tissues using immunohistochemistry analysis, and then conducted the in vitro experiments to verify the role of ACE2 in the migration and proliferation of CRC cells. We found that ACE2 was highly expressed in CRC tissues compared with adjacent normal tissues, and that CRC patients with high ACE2 expression levels showed poor survival. Additionally, combined bioinformatics and qRT-PCR analysis identified a strong negative correlation between ACE2 expression and natural killer cell infiltration in CRC. Meanwhile, ACE2 expression was significantly elevated in patients resistant to anti-CTLA-4 and anti-PD-L1 therapy and was linked to poor prognosis. In vitro experiments showed that silencing ACE2 inhibits the proliferation and invasion of CRC cells. These results highlight ACE2’s involvement in CRC pathogenesis and cancer-immune interactions, positioning it as a promising prognostic and therapeutic biomarker in CRC.

Transfer RNA-derived small RNAs (tsRNAs) play crucial regulatory roles in tumour biology; however, their potential as biomarkers for colorectal cancer (CRC) remains underexplored. Plasma samples from 123 patients with CRC and 79 healthy controls (HCs) were collected for this study. Exosomes were extracted from plasma, validated, and tRF-3004a levels were detected using quantitative real-time polymerase chain reaction (qRT-PCR). The correlation between plasma-derived exosomal tRF-3004a expression levels and clinicopathological parameters was analysed using the chi-square test. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of plasma-derived exosomal tRF-3004a. The results showed that compared with HCs, plasma-derived exosomal tRF-3004a was significantly elevated in patients with CRC and decreased after surgery. Moreover, high tRF-3004a expression was significantly associated with lymph node metastasis, tumour node-metastasis staging, carcinoembryonic antigen (CEA) levels, and nerve/vascular invasion in patients with CRC. ROC analysis revealed that plasma-derived exosomal tRF-3004a demonstrated promising diagnostic utility for CRC, with an area under the curve (AUC) of 0.819 (sensitivity, 0.691; specificity, 0.861). The combination of CEA and carbohydrate antigen 19 − 9 (CA19-9) levels increased the AUC to 0.867. The results of this study demonstrate that plasma-derived exosomal tRF-3004a may serve as a novel diagnostic biomarker for CRC.

Metastasis is a critical feature of malignant tumors and a major cause of treatment failure and poor prognosis. This complex process primarily involves the rearrangement of the cytoskeleton. Among several cytoskeleton‑associated signaling pathways, the ras homolog family (Rho) and Rho‑associated coiled‑coil containing protein kinase (ROCK) signaling pathway serves a key role in cytoskeleton regulation as it controls intracellular actin dynamics and cytoskeletal remodeling to mediate cell movement. Long non‑coding RNAs (lncRNAs), known to serve important roles in tumorigenesis and metastasis, have been shown to regulate the Rho/ROCK pathway. lncRNAs modulate the Rho/ROCK pathway by sponging microRNAs or directly binding to proteins, thereby mediating tumor metastasis. Additionally, lncRNAs can be encapsulated in exosomes and transferred from donor cells to recipient cells, where they regulate components of the Rho/ROCK signaling pathway and further promote the metastatic potential. Based on their functional significance, Rho/ROCK signaling pathway‑associated lncRNAs may serve as novel tumor biomarkers and therapeutic targets. The present review summarizes the role and mechanism of Rho/ROCK signaling pathway‑associated lncRNAs in tumor metastasis, which may offer novel avenues for the diagnosis and treatment of metastatic cancer.

Kidney renal clear cell carcinoma (KIRC) is a highly aggressive malignant tumor, and its occurrence and progression are influenced by tumor microenvironment (TME). CD159A, a natural killer (NK) cell inhibitory receptor, has emerged as a critical immune checkpoint in TME. We conducted a comprehensive multi-omics analysis of CD159A expression, prognostic significance, and functional enrichment in KIRC. Additionally, quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) were employed to perform CD159A expression in the Xiangya KIRC validation cohort. Furthermore, in vitro experiments were evaluated through cell proliferation, colony formation, and flow cytometry (FC) analysis of apoptosis in KIRC cell lines. Our study found that CD159A expression was significantly upregulated in KIRC tissues compared to normal tissues, as confirmed by TCGA data and the Xiangya KIRC validation cohort. In machine learning analyses, the biological significance of the regulatory network risk factors of the CD159A-HLA-E pathway is immunosuppressive receptors or abnormal antigen presentation that may promote immune escape. Elevated CD159A levels were observed in NK cells and CD8⁺ T cells infiltrating KIRC by single-cell RNA sequencing analysis. A positive correlation between CD159A and NK/CD8⁺ T cell infiltration was observed, and higher CD159A expression in KIRC patients receiving anti-PD-1/PD-L1 immunotherapy was associated with improved outcomes. In vitro experiments demonstrated that silencing CD159A significantly suppressed proliferation, colony formation and induced apoptosis in KIRC cells. Our research highlights the critical role of CD159A as a key immune checkpoint in KIRC progression and immune evasion, suggesting its potential as a prognostic and immunotherapy biomarker.

The incidence of breast cancer continues to increase annually, posing a significant challenge for countries worldwide in terms of its prevention and treatment. Therefore, identifying novel therapeutic targets for breast cancer is urgently needed. The peroxiredoxin (PRDX) family is regarded as a good diagnostic marker for various tumors. However, the expression and prognostic significance of PRDX family members in breast cancer remain unclear and require systematic investigation. By using bioinformatic tools such as UALCAN, TIMER2.0, Human Protein Atlas Project (HPA), Gene Set Cancer Analysis (GSCA), and the cBioportal database, we systematically analyzed the expression pattern, prognostic value, methylation status and immune infiltrating association of PRDX gene family members in breast cancer. Through comprehensive analysis, we found that PRDX4 has good prognostic value and is closely related to immune infiltration, and further exploration of its oncogenic function in breast cancer is warranted. Subsequently, we performed a series of cellular assays to explore the potential role of PRDX4 in the progression of breast cancer. We demonstrated that PRDX4 promoted the proliferation, invasion, metastasis, and inhibited the apoptosis of breast cancer cells. In addition, PRDX4 expression was associated with the half maximal inhibitory concentration (IC₅₀) of neratinib which primarily targets human epidermal growth factor receptor 2 (HER2) and showed good binding in molecular docking. Our subsequent experiments showed that the PRDX4-HER2 axis may serve as a potential combined target for neratinib therapy. Our findings suggest that PRDX4 may be a potential diagnostic and prognostic marker for breast cancer, and targeting PRDX4 could represent a novel strategy to improve the efficacy of targeted therapy for patients with HER2-positive breast cancer.