Xiaomin Li

LIM domain-containing protein 2 (LIMD2) is known to promote metastasis in several cancers. However, its role and underlying mechanisms in colon cancer remain unclear. This study focused on investigating the prognostic value, functional impact, and molecular mechanisms of LIMD2 in colon cancer. LIMD2 expression in colon cancer tissues and matched non-cancerous tissues was detected using RT-qPCR and immunohistochemistry. The chi-square test was used to assess the association between LIMD2 expression and clinicopathological characteristics. Kaplan-Meier survival analysis and Cox proportional hazards models were applied to evaluate the prognostic value of LIMD2. The functional role of LIMD2 in colon cancer cell migration was examined through Transwell and wound healing assays. Additionally, RNA sequencing (RNA-seq), co-immunoprecipitation (CoIP), silver staining, and mass spectrometry were performed to uncover the role of LIMD2 in colon cancer cell migration. LIMD2 expression was significantly increased in colon cancer samples and cell lines. High LIMD2 expression was positively correlated with lymph node metastasis and TNM stage. Patients with elevated LIMD2 expression exhibited poorer overall survival (OS). Gain-of-function assays demonstrated that LIMD2 accelerated colon cancer cell migration. RNA-seq analysis revealed that LIMD2 regulates ECM-receptor interactions and focal adhesion pathways. Furthermore, CoIP and mass spectrometry identified cofilin1 as a LIMD2-interacting protein. Our findings indicate that LIMD2 serves as a novel prognostic biomarker and potential target for colon cancer treatment.

The efficacy of 5-fluorouracil treatment for colorectal cancer (CRC) is substantially compromised by drug resistance, although the underlying mechanisms remain unclear. In this research, we aimed to explore the role and mechanism of action of CXC motif chemokine ligand 5 (CXCL5) in 5-fluorouracil resistance. RNA sequencing was conducted to detect abnormally expressed genes in the 5-fluorouracil-resistant colon cancer cell line, HCT8-5FU. CXCL5 expression in CRC tissues and cell lines was evaluated using RT-qPCR, western blotting, and immunohistochemistry. In vivo and in vitro assays were conducted to evaluate the role of CXCL5 in the promotion of CRC progression. Mass spectrometry and co-immunoprecipitation were employed to investigate the role of CXCL5 in CRC development and 5-fluorouracil resistance. Immunofluorescence and western blot analyses were employed to determine the subcellular localization of CXCL5 and its associated signaling pathways. CXCL5 expression was elevated in both CRC tissues and cell lines. CXCL5 promoted CRC cell growth and resistance to 5-fluorouracil in both in vitro and in vivo settings. Mechanistically, CXCL5 may modulate the MDM2/p53 axis to inhibit p21 by binding to RALY. In this study, CXCL5 accelerated CRC progression and increased CRC cell resistance to 5-fluorouracil via the inhibition of p21 expression. Thus, CXCL5 is a potential target for CRC therapeutic strategies.

Karyopherin nuclear transport receptors play important roles in tumour development and drug resistance and have been reported as potential biomarkers and therapeutic targets for tumour treatment. However, IPO5, one of the karyopherin nuclear transport receptor family members, remains largely uncharacterized in tumour progression. The TCGA data, quantitative reverse transcription-PCR (qRT-PCR), western blotting, and IHC analyses were used to detect IPO5 expression in CRC tissues. A series of in vivo and in vitro experiments was utilized to demonstrate the function of IPO5 in CRC tissues. Mass spectrometry (MS), CO-IP technology, subcellular fractionation, and immunofluorescence were utilized to investigate the possible mechanisms of CRC. IPO5 was highly expressed and positively correlated with the clinicopathological characteristics of colorectal cancer tissues. Functional experiments indicated that IPO5 could promote the development of CRC. Mechanistically, we screened RASAL2, one cargo of IPO5, and further confirmed that IPO5 bound to the NLS sequence of RASAL2, mediating RASAL2 nuclear translocation and inducing RAS signal activation, thereby promoting the progression of CRC. Together, our results indicate that IPO5 is overexpressed in colorectal cancer cells. By transporting RASAL2, IPO5 may play a crucial role in CRC.

Circular RNAs (circRNAs) are significantly dysregulated in various cancer types. However, the roles and mechanisms of circRNAs in cancer remain largely unknown. In this study, we demonstrated that a novel circRNA (circITGA7) and its linear host gene ITGA7 are both significantly downregulated in colorectal cancer (CRC) tissues and cell lines. These decreased expression levels correlated with CRC progression. Functional assays demonstrated that ectopic circITGA7 expression suppressed the growth and metastasis of CRC cells in vitro and in vivo. Knockdown of circITGA7 or ITGA7 promoted the proliferation and migration of CRC cells in vitro, and enhanced CRC growth in vivo. Mechanistically, by using RNA‐sequencing and KEGG enrichment analysis, we found that circITGA7 is a negative regulator of the Ras signalling pathway, and that ITGA7 is associated with cytokine‐related signalling pathways. In addition, circITGA7 binds to miR‐370‐3p to antagonise its suppression of neurofibromin 1, which is a well‐known negative regulator of the Ras pathway. Finally, circITGA7 upregulates the transcription of ITGA7 by suppressing RREB1 via the Ras pathway. In conclusion, our findings indicate a suppressor role of circITGA7 and ITGA7 in CRC, and reveal that circITGA7 inhibits the proliferation and metastasis of CRC cells by suppressing the Ras signalling pathway and promoting the transcription of ITGA7, suggesting that circITGA7 is a potential target for CRC treatment. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Background: Recent studies have revealed that circular RNAs are involved in the biological process of some kinds of human cancers. However, little is known about their diagnostic values and functions in colorectal cancer (CRC).Methods: The expression levels of hsa_circ_0000567 in 102 paired CRC tissues and adjacent noncancerous tissues, 5 CRC cell lines, and a normal colorectal epithelial cell line were detected by quantitative real‐time polymerase chain reaction (qRT‐PCR). The correlations between hsa_circ_0000567 expression levels and the clinicopathological factors of patients with CRC were analyzed. Furthermore, the loss‐of‐function assay was performed to investigate the functions of hsa_circ_0000567 in vitro. Finally, a receiver operating characteristic (ROC) curve was established to evaluate the diagnostic value of hsa_circ_0000567.Results: Hsa_circ_0000567 expression was significantly downregulated in CRC tissues and CRC cell lines. In addition, the decreased hsa_circ_0000567 expression in CRC was negatively correlated with tumor size (P = .011), lymph metastasis (P = .003), distal metastasis (P < .0001), and tumor–node–metastasis (TNM) stage (P = .003) in CRC. Moreover, knockdown of hsa_circ_0000567 promoted CRC cells proliferation and migration in vitro. Importantly, the area under the ROC curve (AUC) was 0.8653, which indicates hsa_circ_0000567 can serve as a diagnostic biomarker.Conclusion: Hsa_circ_0000567 may be a novel suppressor and a potential diagnosis biomarker in CRC.