Paeoniflorin (PF) exhibits tumor suppressive functions in a variety of human cancers. However, the function of PF and molecular mechanism in colorectal cancer are elusive. In the present study, we investigated whether PF could exert its antiproliferative activity, anti-migration, and anti-invasive function in colorectal cancer cells. We found that PF inhibited cell growth and induced apoptosis and blocked cell cycle progression in the G0/G1 phase in colorectal cancer cells. Moreover, we found that PF suppressed cell migration and invasion in colorectal cancer cells. FoxM1 has been reported to play an important oncogenic role in human cancers. We also determine whether PF inhibited the expression of FoxM1, leading to its anti-cancer activity. We found that PF treatment in colorectal cancer cells resulted in down-regulation of FoxM1. The rescue experiments showed that overexpression of FoxM1 abrogated the tumor suppressive function induced by PF treatment. Notably, depletion of FoxM1 promoted the anti-tumor activity of PF in colorectal cancer cells. Therefore, inhibition of FoxM1 could participate in the anti-tumor activity of PF in colorectal cancer cells.

This study aimed to investigate the role of circ0106714-miR-942-5p-discs large homolog 2 (DLG2), a novel interactome, in colorectal cancer (CRC). Circ0106714 was found to be the most significantly downregulated circular RNA in CRC using a bioinformatics method, and we researched whether the ability of circ0106714 to sponge miR-942-5p and release DLG2 could affect CRC development via Hippo-YES-associated protein (YAP) signaling. We first employed qRT-PCR and immunoblotting to detect messenger RNA (mRNA) and protein expression, respectively. Live imaging of mice tumor xenografts was then conducted to study the effect of circ0106714 on tumor progression in vivo. Reporter gene assays were subsequently conducted to verify the predicted targeting relationship between circ0106714, miR-942-5p, and DLG2 mRNA in SW480 and HCT116 cell lines. As well as using flow cytometry for both apoptosis and cell cycle profile analyses, CCK-8 and clone foci formation assays were performed to assess cell survival. Wound healing assay and transwell invasion assay were later carried out to evaluate the migration and invasion of the cell lines. Findings revealed that circ0106714 and DLG2 were significantly downregulated, while miR-942-5p was significantly upregulated in human CRC tissues and cell lines. However, circ0106714 upregulation significantly suppressed tumor progression in vivo and inhibited the malignancy phenotypes of tumor cells in vitro by targeting miR-942-5p. Also discovered in this research was that miR-942-5p could directly target DLG2 mRNA, thus enhancing the malignancy phenotypes of CRC cells. We even found that DLG2 overexpression resulted in enhanced phosphorylation of YAP, a critical downstream effector of DLG2. This downstream effector was demonstrated to have a tumor-suppressive capacity in CRC cell lines. In sum, circ0106714 could suppress CRC by sponging miR-942-5p and releasing DLG2, thus promoting YAP phosphorylation.

PurposeThis study aimed to evaluate the short- and long-term outcomes of laparoscopic hepatectomy (LH) for colorectal liver metastases (CRLM) in elderly patients.Patients and methodsBetween January 2009 and January 2016, LH was performed for 241 consecutive patients who were ≥60 years old and had CRLM. Based on their age at the LH, the patients were divided into an elderly group (≥70 years old, 78 patients) and a middle-aged group (60–69 years old, 163 patients). The short- and long-term outcomes were compared between the two groups.ResultsCompared to the middle-aged group, the elderly group had higher values for Charlson comorbidity index, proportion of preoperative chemotherapy, and American Society of Anesthesiologists score. No other significant differences were observed in the preoperative characteristics. The elderly group had a higher conversion rate, compared to the middle-aged group, although no significant differences were observed in the surgical procedures, surgical times, intraoperative blood losses, numbers and severities of postoperative 90-day complications, postoperative 90-day mortality rates, pathology results, and other short-term outcomes. Long-term follow-up revealed similar rates of recurrence, disease-free survival, and overall survival in the two groups. Multivariable analysis revealed that age did not independently predict overall survival or disease-free survival.ConclusionSimilar short- and long-term outcomes were observed after LH for CRLM in elderly and middle-aged patients. Thus, advanced age is not a contraindication for LH treatment in this setting.

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Background: Most recently, long non-coding RNAs (lncRNAs) emerge as crucial modulators in many biological processes, such as embryonic development, cell growth, and tumorigenesis. However, the correlations between lncRNAs and colorectal cancer (CRC) cell proliferation, metastasis, and gemcitabine resistance are not well understood. Results: The expression of AGAP2-AS1 was overexpressed in CRC tissues and negatively correlated with the survival of patients with CRC. AGAP2-AS1 promoted CRC cell proliferation and inhibited apoptosis. Moreover, AGAP2-AS1 enhanced the chemoresistance of CRC cells to gemcitabine. In addition, AGAP2-AS1 enhanced the migration and invasion of CRC cells. Mechanistic studies showed that AGAP2-AS1 regulated fibroblast growth factor receptor 1 (FGFR1) expression by sponging miR-497 in CRC progression. Conclusion: We identified an oncogenic role of AGAP2-AS1 in the development and progression of CRC. Methods: qRT-PCR was used to measure the expression of AGAP2 Antisense RNA 1 (AGAP2-AS1) in 116 cases of CRC and adjacent normal tissues. Luciferase reporter assays was used to detect the interaction between AGAP2-AS1 and miR-497. The xenograft tumor experiment was used to study the in vivo function of AGAP2-AS1.

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Background Immunotherapy has been recently established as a new direction for the treatment of colorectal cancer (CRC), a gastrointestinal cancer. In this investigation, we aimed to expound how the posttranscriptional regulation modulated by microRNA-222 (miR-222) from mesenchymal stem cells-derived extracellular vesicles (MSC-EVs) affected the AKT pathway and the immune escape in CRC. Methods CRC cell malignant phenotype, including proliferation, migration, invasion, and apoptosis, was firstly detected after co-culture with MSC-EVs. miRNAs with differential changes in CRC cells before and after EVs treatment were filtered by microarray analysis. miR-222 was then downregulated to examine its role in CRC cells in response to EVs. Cells were implanted in mice to induce xenograft tumors, and infiltrating T cells was assessed by immunohistochemistry. The mRNA microarray was used to screen target genes, followed by rescue experiments. ChIP and western blot were conducted to validate the downstream biomolecule of ATF3. Results After treatment of CRC cells with MSC-EVs, the expression of miR-222 was upregulated, and cell activity was increased. Inhibition of miR-222 decreased CRC malignant aggressiveness in vitro and reduced tumorigenesis and immune escape in vivo. miR-222 targeted and bound to ATF3. Downregulation of ATF3 enhanced CRC cell malignant aggressiveness, tumorigenic capacity and immune escape. Mechanistically, ATF3 inhibited AKT1 transcription and mediated the AKT pathway. Conclusion MSC-EVs carry miR-222 to promote CRC cell malignant aggressiveness and immune escape. miR-222 targets and binds to ATF3, which inhibits AKT1 transcriptional activity and thereby mediates the AKT pathway.