Background: Circular RNAs (circRNAs) generated by back‐splicing of precursor mRNAs (pre‐mRNAs) are often aberrantly expressed in cancer cells. Accumulating evidence has revealed that circRNAs play a critical role in the progression of several cancers, including colorectal cancer (CRC). However, the current understandings of the emerging functions of circRNAs in CRC lipid metabolism and the underlying molecular mechanisms are still limited. Here, we aimed to explore the role of circCAPRIN1 in regulating CRC lipid metabolism and tumorigenesis. Methods: circRNA microarray was performed with three pairs of tumor and non‐tumor tissues from CRC patients. The expression of circRNAs were determined by quantitative PCR (qPCR) and in situ hybridization (ISH). The endogenous levels of circRNAs in CRC cells were manipulated by transfection with lentiviruses overexpressing or silencing circRNAs. The regulatory roles of circRNAs in the occurrence of CRC were investigated both in vitro and in vivo using gene expression array, RNA pull‐down/mass spectrometry, RNA immunoprecipitation assay, luciferase reporter assay, chromatin immunoprecipitation analysis, and fluorescence in situ hybridization (FISH). Results: Among circRNAs, circCAPRIN1 was most significantly upregulated in CRC tissue specimens. circCAPRIN1 expression was positively correlated with the clinical stage and unfavorable prognosis of CRC patients. Downregulation of circCAPRIN1 suppressed proliferation, migration, and epithelial‐mesenchymal transition of CRC cells, while circCAPRIN1 overexpression had opposite effects. RNA sequencing and gene ontology analysis indicated that circCAPRIN1 upregulated the expressions of genes involved in CRC lipid metabolism. Moreover, circCAPRIN1 promoted lipid synthesis by enhancing Acetyl‐CoA carboxylase 1 (ACC1) expression. Further mechanistic assays demonstrated that circCAPRIN1 directly bound signal transducer and activator of transcription 2 (STAT2) to activate ACC1 transcription, thus regulating lipid metabolism and facilitating CRC tumorigenesis. Conclusions: These findings revealed the oncogenic role and mechanism of circCAPRIN1 in CRC. circCAPRIN1 interacted with STAT2 to promote CRC tumor progression and lipid synthesis by enhancing the expression of ACC1. circCAPRIN1 may be considered as a novel potential diagnostic and therapeutic target for CRC patients.

Background: Low anterior resection syndrome (LARS) is a series of bowel dysfunction symptoms, including altered bowel frequency, irregular bowel rhythms, fecal incontinence, and constipation. LARS occurs in 80% of patients undergoing sphincter-preserving surgery, affecting patients’ quality of life along with social avoidance. Different measurements and treatments have been raised to deal with LARS, but no systematic standard has been developed. Objective and Methods: To promote the standardization of clinical trials and clinical management of LARS, this review summarizes the latest findings up until 2023 regarding the diagnostic criteria, assessment protocols, and treatment modalities for postoperative LARS in rectal cancer. Results: The diagnostic criteria for LARS need to be updated to the definition proposed by the LARS International Collaborative Group, replacing the current application of the LARS score. In both clinical trials and clinical treatment, the severity of LARS should be assessed using at least one symptom assessment questionnaire, the LARS score or MSKCC BFI, and at least one scale related to quality of life. Anorectal manometry, fecoflowmetry, endoscopic ultrasonography, and pelvic floor muscle strength testing are recommended to be adopted only in clinical trials. After analysis of the latest literature on LARS treatment, a stepwise classification model is established for the standardized clinical management of LARS. Patients with minor LARS can start with first-line treatment, including management of self-behavior with an emphasis on diet modification and medication. Lamosetron, colesevelam hydrochloride, and loperamide are common antidiarrheal agents. Second-line management indicates multi-mode pelvic floor rehabilitation and transanal irrigation. Patients with major LARS should select single or several treatments in second-line management. Refractory LARS can choose antegrade enema, neuromodulation, or colostomy. Conclusions: In clinical trials of LARS treatment between 2020 and 2022, the eligibility criteria and evaluation system have been variable. Therefore, it is urgent to create a standard for the diagnosis, assessment, and treatment of LARS. Failure to set placebos and differentiate subgroups are limitations of many current LARS studies. Randomized controlled trials comparing diverse therapies and long-term outcomes are absent, as well. Moreover, a new scale needs to be developed to incorporate the patient’s perspective and facilitate outpatient follow-up. Though the establishment of a stepwise classification model for LARS treatment here is indispensable, the refinement of the guidelines may be improved by more standardized studies.

Synthetic immunosuppressive glucocorticoids (GCs) are widely used to control inflammatory bowel disease (IBD). However, the impact of GC signaling on intestinal tumorigenesis remains controversial. Here, we report that intestinal epithelial GC receptor (GR), but not whole intestinal tissue GR, promoted chronic intestinal inflammation-associated colorectal cancer in both humans and mice. In patients with colorectal cancer, GR was enriched in intestinal epithelial cells and high epithelial cell GR levels were associated with poor prognosis. Consistently, intestinal epithelium–specific deletion of GR (GR iKO) in mice increased macrophage infiltration, improved tissue recovery, and enhanced antitumor response in a chronic inflammation–associated colorectal cancer model. Consequently, GR iKO mice developed fewer and less advanced tumors than control mice. Furthermore, oral GC administration in the early phase of tissue injury delayed recovery and accelerated the formation of aggressive colorectal cancers. Our study reveals that intestinal epithelial GR signaling repressed acute colitis but promoted chronic inflammation–associated colorectal cancer. Our study suggests that colorectal epithelial GR could serve as a predictive marker for colorectal cancer risk and prognosis. Our findings further suggest that, although synthetic GC treatment for IBD should be used with caution, there is a therapeutic window for GC therapy during colorectal cancer development in immunocompetent patients.

Late recurrence (5 or more years) after radical resection of colorectal cancer (CRC) is rare. This study aims to investigate the features of late recurrence in stage I–III CRC. A total of 9,754 stage I–III patients with CRC who underwent radical surgery without receiving neoadjuvant therapy, at the Fudan University Shanghai Cancer Center (FUSCC), were enrolled in this study. These patients were divided into three groups: early recurrence (3 months−2 years), intermediate recurrence (2–5 years), and late recurrence (over 5 years). The median duration of follow-up was 53.5 ± 30.1 months. A total of 2,341 (24.0%) patients developed recurrence. The late recurrence rate was 11.7%. Patients with a higher risk of late recurrence were more likely to be older, to be at the T4 stage, to have a higher degree of colon cancer, to have a lower frequency of signet ring cell carcinoma, to have fewer poorly differentiated tumors, to be at the early stage of CRC, along with less perineural and vascular invasions. Multivariate logistic regression analysis identified age, differentiation, T stage, N stage, perineural, and vascular invasions as independent factors for late recurrence. Late recurrent CRC has some distinctive characteristics. Although recurrence over 5 years after surgery is infrequent, an enhanced follow-up is still needed for the selected patients after 5 years.