No abstract

MiR-21, the only microRNA (miRNA) found to be overexpressed in any type of solid tumor, its guide stand, miR-21-5p, has been studied a lot in colorectal cancer (CRC); however, few researchers focused on its passenger strand, miR-21-3p. In our study, based on The Cancer Genome Atlas (TCGA) data, we found that there were more varieties and quantities of miR-21-3p isoforms in microsatellite instability (MSI)-type CRC. We further examined the role of miR-21-3p by in vitro and in vivo studies. MiR-21-3p may be an oncogene in CRC by promoting cellular mobility through epithelial-mesenchymal transition. However, different isoforms, especially miR-21-3p 0 | 2, may be a favorable prognostic marker for CRC survival, probably due to increased complementary effect of miR-21-5p and/or target genes. Further study investigating the underlying mechanism of miRNA isoforms is needed.

As a newly discovered cytokine, interleukin 9 was initially considered a T-lymphocyte growth factor. Interleukin 9 affects target cells by binding to a member of the γc-family of receptors and is involved in inflammation, autoimmune diseases, and other ailments. In recent years, mounting evidence reveals that interleukin 9 exerts antitumor effects, which has attracted considerable attention. Many previous studies were performed in vivo by establishing a mouse model of melanoma. Here, interleukin 9 protein and messenger RNA expression levels were both low in colon carcinoma tissue specimens, as assessed by immunohistochemistry and quantitative real-time polymerase chain reaction. In addition, interleukin 9 expression in these samples was correlated with TNM staging, Dukes staging, lymph node metastasis, and good prognosis, but not with gender, age, tumor size, tumor differentiation, and hepatic metastasis. In vivo, by establishing a mouse subcutaneous allograft model, we found that interleukin 9 overexpression inhibited tumor growth and resulted in longer survival time. Then, antitumor immune responses were increased by interleukin 9 as demonstrated by flow cytometry. Furthermore, interleukin 9 was shown to exert antitumor effects by regulating T-cell function and killing tumor cells in the tumor microenvironment. Overall, this study revealed that interleukin 9 exerts robust antitumor effects in colon cancer and transforms the tumor microenvironment in vivo.

Originally identified as an E3 ligase regulating toll-like receptor (TLR) signaling, ring finger protein 216 (RNF216) also plays an essential role in autophagy, which is fundamental to cellular homeostasis. Autophagy dysfunction leads to an array of pathological events, including tumor formation. In this study, we found that RNF216 was upregulated in human colorectal cancer (CRC) tissues and cell lines, and was associated with progression of CRC. RNF216 promoted CRC cell proliferation and migration in vitro and in vivo, largely by enhancing proteasomal degradation of BECN1, a key autophagy regulator and tumor suppressor. RNF216 restricted CRC cell autophagy through BECN1 inhibition under nutritional starvation conditions. RNF216 knockdown increased the autophagy, limiting CRC cell proliferation and migration. Moreover, BECN1 knockdown or autophagy inhibition restored proliferation and migration of RNF216-knockdown CRC cells. Collectively, our results suggested that RNF216 promoted CRC cell proliferation and migration by negatively regulating BECN1-dependent autophagy. This makes RNF216 as a potential biomarker and novel therapeutic target for inhibiting CRC development and progression.

Increasing research has indicated that absent in melanoma 2 (AIM2) is aberrantly expressed in several tumor types. However, the association between AIM2 expression and clinicopathological factors or prognosis of patient with colorectal cancer (CRC) remains elusive. In the present study, we first examined the protein and mRNA expression of AIM2 in CRC cell lines by western blotting and quantitative RT-PCR (qRT-PCR). Then, we detected AIM2 expression in CRC tissue using western blotting and immunohistochemistry (IHC) respectively to evaluate its clinicopathological characteristics and prognosis in CRC. Our cytological experiments showed that there was low AIM2 expression in most of the CRC cell lines. Western blotting and IHC indicated that AIM2 expression was obviously lower in the primary CRC tissue than the adjacent normal tissue (P<0.01 and P<0.001). Clinicopathological analysis revealed that low AIM2 expression was significantly associated with some clinicopathological features such as depth of invasion (P=0.020), TNM clinical stage (P=0.013) and lymph node metastasis (P=0.026). Spearman analysis indicated that there was a negative correlation between AIM2 expression and preoperative serum carcino-embryonic antigen (CEA) levels in CRC patients (r=-0.217, P=0.009). Moreover, Kaplan-Meier analysis showed that low expression of AIM2 could lead to a significantly shorter overall survival rate (P=0.001). Cox's proportional hazards model also indicated that the low expression of AIM2 could serve as an independent and significant prognostic factor for survival. Taken together, our findings identify AIM2 as a valuable biomarker for prognosis and a potential therapeutic target for CRC.