Abnormal accumulation of lipids has been highlighted in the progression of clear cell renal cell carcinoma (ccRCC). However, the underlying mechanism remains unclear. Emerging evidence suggests long noncoding RNAs (lncRNAs) participate in the regulation of lipid metabolism. In this study, we found lncRNA COL18A1-AS1 was downregulated in ccRCC and that higher COL18A1-AS1 expression indicated better prognosis. Decreased COL18A1-AS1 expression was caused by DNA methylation at the CpG islands within its promoter. Restoring the epigenetically silenced COL18A1-AS1 repressed tumor progression, promoted lipid browning and consumption in vitro and in vivo. Mechanistically, COL18A1-AS1 could competitively bind miR-1286 to increase the expression of Krüppel-like factor 12 (KLF12). Downregulation of COL18A1-AS1 in ccRCC resulted in the low expression of KLF12. COL18A1-AS1/KLF12 positively regulated uncoupling protein 1 (UCP1)–mediated lipid browning, which promotes tumor cell “slimming” and inhibits tumor progression. When tumor cell “slimming” occurred, lipid droplets turned into tiny pieces, and lipids were consumed without producing ATP energy. Taken together, our findings on COL18A1-AS1-miR-1286/KLF12 axis revealed a potential mechanism of abnormal accumulation of lipids in ccRCC and could be a promising therapeutic target for ccRCC patients.

Obstructions can occur during any stage of colorectal cancer and correspond with poor prognosis. Obstructive colorectal cancer (OCRC) is harder and exhibits increased tumor budding and proliferation of myofibroblasts compared with nonobstructive colorectal cancer, suggesting that the occurrence of obstruction may be related to extracellular matrix (ECM) remodeling. In this study, we found that colorectal cancer and OCRC samples differed substantially in ECM composition, specifically in collagen (newly formed and mature) and proteoglycans (including glycosaminoglycan, hyaluronic acid, and chondroitin sulfate). OCRC also exhibited considerable changes in ECM biomechanics and collagen arrangement. Interestingly, OCRC samples presented a notable increase in matrix cancer-associated fibroblasts (mCAF). The abundance of mCAFs correlated with the accumulation of palmitic acid (PA), and high concentrations of PA increased the secretion of ECM-related proteins by mCAFs. Additionally, PA did not directly affect normal fibroblasts but rather activated the NF-κB pathway in tumor cells to stimulate secretion of CSF1, TGFβ1, and CXCL8, which promoted the activation of normal fibroblasts into mCAFs and exacerbated ECM stiffening. Drug screening with a natural compound library identified vanillylacetone as a potential inhibitor of PA-induced cytokine secretion and ECM stiffening. These findings highlight intratumoral PA accumulation as a key mechanism driving ECM alterations and OCRC progression and suggest that targeting this axis may be useful for treating patients with colorectal cancer with risk of obstruction. Significance: Palmitic acid accumulation activates the NF-κB pathway in colorectal cancer cells to promote cytokine secretion that facilitates the generation of matrix cancer-associated fibroblasts, driving extracellular matrix remodeling and development of obstructions.

Colorectal cancer poses a significant threat to human health due to its high aggressiveness and poor prognosis. Key factors impacting patient outcomes include post-surgical recurrence, chemotherapeutic drug resistance, and insensitivity to immunotherapy. Consequently, early diagnosis and the development of effective targeted therapies are essential for improving prevention and treatment strategies. Inorganic nanomaterials have gained prominence in the diagnosis and treatment of colorectal cancer owing to their unique size, advantageous properties, and high modifiability. Various types of inorganic nanomaterials—such as metal-based, metal oxide, quantum dots, magnetic nanoparticles, carbon-based, and rare-earth nanomaterials—have demonstrated significant potential in enhancing multimodal imaging, drug delivery, and synergistic therapies. These advancements underscore their critical role in improving therapeutic outcomes. This review highlights the properties and development of inorganic nanomaterials, summarizes their recent applications and progress in colorectal cancer diagnosis and treatment, and discusses the challenges in translating these materials into clinical use. It aims to provide valuable insights for future research and the clinical application of inorganic nanomaterials in colorectal cancer management.

The accuracy of intraoperative localization of tumors undetectable under optical visualization determines surgical quality and survival outcomes in gastrointestinal cancers. Current approaches, however, remain constrained by suboptimal spatial resolution and low procedural efficiency. Additionally, conventional electromagnetic localization techniques based on image registration face challenges in soft tissue deformation scenarios. Here, we developed an electromagnetic localization technology for intraluminal tumor localization based on injectable magnetic hydrogel with sustained magnetization properties (MagLabel-IH). Following endoscopic injection into the gastrointestinal tract and in situ realignment, MagLabel-IH enables continuous intraluminal magnetic signal tracing. Intraoperatively, a dynamic registration framework synchronizes the magnetic coordinate system with real-time anatomical positions under visual guidance, achieving precise localization of optically invisible intraluminal tumors. The system demonstrated exceptional surgical instrument maneuverability (e.g., tissue grasping, resection path selection) during MagLabel-IH detection. In vivo animal evaluations demonstrated significantly enhanced localization accuracy compared to conventional biological dyes tattooing (3.8 ± 0.8 mm vs. 16.8 ± 8.6 mm, P < 0.05). Furthermore, the magnetic labels-based localization system exhibited promising utility for tumor margin demarcation and planning of gastrointestinal functional reconstruction.