Small non-coding RNAs are widespread in the biological world and have been extensively explored over the past decades. Their fundamental roles in human health and disease are increasingly appreciated. Furthermore, a growing number of studies have investigated the functions of small non-coding RNAs in cancer initiation and progression. In this review, we provide an overview of the biogenesis of small non-coding RNAs with a focus on microRNAs, PIWI-interacting RNAs, and a new class of tRNA-derived small RNAs. We discuss their biological functions in human cancer and highlight their clinical application as molecular biomarkers or therapeutic targets.

Pancreatic ductal adenocarcinoma (PDAC) has earned a notorious reputation as one of the most formidable and deadliest malignant tumors. Within the tumor microenvironment, cancer cells have acquired the capability to maintain incessant expansion and increased proliferation in response to hypoxia via metabolic reconfiguration, leading to elevated levels of lactate within the tumor surroundings. However, there have been limited studies specifically investigating the association between hypoxia and lactic acid metabolism-related lactylation in PDAC. In this study, multiple machine learning approaches, including LASSO regression analysis, XGBoost, and Random Forest, were employed to identify hub genes and construct a prognostic risk signature. The implementation of the CERES score and single-cell analysis was used to discern a prospective therapeutic target for the management of PDAC. CCK8 assay, colony formation assays, transwell, and wound-healing assays were used to explore both the proliferation and migration of PDAC cells affected by CENPA. In conclusion, we discovered two distinct subtypes characterized by their unique hypoxia and lactylation profiles and developed a risk score to evaluate prognosis, as well as response to immunotherapy and chemotherapy, in PDAC patients. Furthermore, we indicated that CENPA may serve as a promising therapeutic target for PDAC.

Pancreatic adenosquamous carcinoma (PASC) is a rare pathological subtype of pancreatic cancer (PC), with a worse prognosis than pancreatic ductal adenocarcinoma (PDAC). Due to its rarity, our knowledge of PASC and its biological characteristics are limited. In this review, we provide an overview of the histogenesis, genetic features, diagnosis, treatment, and prognosis of PASC, as well as pancreatic squamous cell carcinoma (PSCC). The information provided here may help to clarify our understanding of PASC and provide useful avenues for further research on this disease.

The tumor microenvironment (TME) plays a vital role in the development, progression, and metastasis of pancreatic cancer (PC). The composition of the TME and its potential prognostic value remains to be fully understood, especially in adenosquamous carcinoma of pancreas (ASCP) patients. Immunohistochemistry was used to explore the clinical significance of CD3, CD4, CD8, FoxP3, and PD-L1 expression within the TME and to identify correlations with the prognosis of PC in a series of 29 patients with ASCP and 54 patients with pancreatic ductal adenocarcinoma (PDAC). Data from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) were accessed to obtain the scRNA-seq data and transcriptome profiles. Seurat was used to process the scRNA-seq data, and CellChat was used to analyze cell–cell communication. CIBERSORT was used to approximate the constitution of tumor-infiltrating immune cell (TICs) profiles. Higher levels of PD-L1 were linked with a shorter overall survival in ASCP (p = 0.0007) and PDAC (p = 0.0594). A higher expression of CD3+ and CD8+ T-cell infiltration was significantly correlated with a better prognosis in PC. By influencing the composition of tumor-infiltrating immune cells (TICs), high levels of PD-L1 expression are linked with a shorter overall survival in ASCP and PDAC.

Background: As a member of the Krüppel-like factor (KLFs) family, Krüppel-like factor 6 (KLF6) plays a critical role in regulating key cellular functions. Presently, scholars have proved the important role of KLF6 in the tumorigenesis of certain cancers through a large number of experiments. However, gaps still remain in our knowledge of the role of KLF6 in pancreatic cancer (PAAD). Therefore, this paper mainly investigates the role of KLF6 in the progression of pancreatic cancer. Methods: The expression pattern of KLF6 in pancreatic cancer was explored in pancreatic cancer tissues and cell lines. Then, we investigated the prognostic value of KLF6 in pancreatic cancer by immunohistochemical assays. Next, Cell Counting Kit-8 (CCK8) and clone information assays were employed to explore the proliferation of PAAD affected by KLF6. The metastasis and epithelial-mesenchymal transition (EMT) abilities affected by KLF6 were identified through transwell invasion as well as migration assays and western blots. Finally, the TRRUST tool was used to analyze the potential targeted genes of KLF6. The results were verified by Quantificational Real-time Polymerase Chain Reaction (qRT-PCR), western blot and rescue assays. Results: KLF6 expresses lowly in pancreatic cancer compared to corresponding normal tissues and relates to poor survival times. Overexpression of KLF6 inhibits the proliferation, metastasis, and EMT progression in pancreatic cancer cells. Further studies suggest that KLF6 could upregulate ATF3 in PAAD. Conclusions: Our results suggest that KLF6 can be a useful factor in predicting the prognosis of PAAD patients and that it inhibits the progression of pancreatic cancer by upregulating activating transcription factor 3 (ATF3).

Background: Members of the nuclear receptor‐binding SET domain (NSD) family of histone H3 lysine 36 methyltransferases comprise NSD1, NSD2 (MMSET/WHSC1), and NSD3 (Wolf–Hirschhorn syndrome candidate 1‐like 1, WHSC1L1). While the expression of NSD genes is essential to normal biological processes and cancer, knowledge of their expression levels to prognosticate in cancer remains unclear.Methods: We analyzed the expression patterns for NSD family genes across multiple cancer types and examined their association with clinical features and patient survival profiles. Next, we explored the association between NSD3 expression and described features of the tumor microenvironment (TME) in PAAD, a severe type of pancreatic cancer. In particular, we correlated promoter methylation levels for NSD3 with patient outcomes in PAAD. Finally, we explored the putative oncogenic roles for NSD3 using a series of experiments with pancreatic cancer cells.Results: We report that the expression of NSD family members is correlated with clinical prognosis across multiple types of cancers. Also, we demonstrate that NSD3 variants are most prevalent among NSD genes across cancers we analyzed. Notably, when compared with NSD1 and NSD2, we find that NSD3 is prominently expressed, and its expression is significantly linked with clinical outcome in pancreatic cancer. Furthermore, NSD3 is frequently amplified, exhibits low promoter methylation, and is correlated with immune cell infiltration and enhanced proliferation of pancreatic cancer. Finally, we demonstrate that knockdown of NSD3 alters H3K36me2 methylation, downstream gene expression and EGFR/ERK signaling in pancreatic cancer cells.Conclusions: We find that expression levels, the presence of genetic variants of NSD family genes, as well as their promoter methylation are correlated with clinical outcomes in cancer, including pancreatic cancer. Our in vitro experiments suggest that NSD3 may be relevant to gene expression regulation and growth factor signaling in pancreatic cancer.