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It has been reported that lncRNA NBR2 regulates cancer metabolism. We investigated the role of NBR2 in colorectal cancer. We found that NBR2 was downregulated in colorectal cancer tissues than in adjacent healthy tissues. Decreased expression levels of NBR2 in tumor tissues were observed with the increase of clinical stages. MiRNA-21 was upregulated in colorectal cancer tissues than in adjacent healthy tissues, and was significantly and inversely correlated with NBR2. NBR2 overexpression downregulated miRNA-21 in colorectal cancer cells, while miRNA-21 overexpression failed to significantly affect NBR2 expression. NBR2 overexpression suppressed migration and invasion of colorectal cancer cells. MiRNA-21 overexpression played an opposite role and attenuated the effects of NBR2 overexpression. NBR2 overexpression did not significantly alter cancer cell proliferation. Therefore, lncRNA NBR2 inhibited colorectal cancer cell migration and invasion possibly by downregulating miRNA-21.

// Rui Zhang 1 , Jian Xu 1 , Jian Zhao 1 and Jinghui Bai 2 1 Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Insititute, Shenyang 110042, China 2 Department of Internal Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Insititute, Shenyang 110042, China Correspondence to: Jinghui Bai, email: lnjinghuibai@sohu.com Keywords: colorectal cancer stem cells, miR-27a, TRAIL, Apaf-1, caspase-9 Received: March 06, 2017 Accepted: March 22, 2017 Published: April 01, 2017 ABSTRACT MicroRNAs have been proved to participate in multiple biological processes in cancers. For developing resistance to cytotoxic drug, cancer cells, especially the cancer stem cells, usually change their microRNA expression profile to survive in hostile environments. In the present study, we found that expression of microRNA-27a was increased in colorectal cancer stem cells. High level of microRNA-27a was indicated to induce the resistance to TNF-related apoptosis-inducing ligand (TRAIL). Knockdown of microRNA-27a resensitized colorectal cancer stem cells to TRAIL-induced cell death. Mechanically, the gene of Apaf-1, which is associated with the mitochondrial apoptosis, was demonstrated to be the target of microRNA-27a in colorectal cancer stem cells. Knockdown of microRNA-27a increased the expression level of Apaf-1, thus enhancing the formation of Apaf-1-caspase-9 complex and subsequently promoting the TRAIL-induced apoptosis in colorectal cancer stem cells. These findings suggested that knockdown of microRNA-27a in colorectal cancer stem cells by the specific antioligonucleotides was potential to reverse the chemoresistance to TRAIL. It may represent a novel therapeutic strategy for treating the colorectal cancer more effectively.

Our study was intended to provide evidence for whether long noncoding RNA (lncRNA) SNHG1 would accelerate the epithelial-mesenchymal transition (EMT) course intrinsic in colorectal cancer (CRC) by sponging downstream miR-497-5p and miR-195-5p. We altogether collected 338 pairs of CRC and noncancerous tissues, and meanwhile purchased five CRC cell lines (i.e., SW480, HCT116, Lovo, CaCO-2, and HT29) and human embryo intestinal mucosal tissue-sourced cell line (i.e., CCC-HIE-2). The CRC cells as mentioned above were appraised regarding their potencies in proliferation, migration, and invasion, after being transfected with pcDNA3.1-SNHG1, si-SNHG1, miR-195-5p mimic/inhibitor, and miR-497-5p mimic/inhibitor. Eventually, we depended on reverse transcription-polymerase chain reaction to assess SNHG1, miR-497-5p, and miR-195-5p expressions, and the protein levels of EMT-specific molecules were determined on the strength of western blotting. It seemed that there was a high potential for highly expressed SNHG1 and lowly expressed miR-497/miR-195 to symbolize CRC patients' unfavorable prognosis (p < .05). Concurrently, CRC cells were detected with higher SNHG1 expression and lower miR-497/miR-195 expression than CCC-HIE-2 cells (p < .05). In addition, the EMT process of CRC cells was facilitated markedly against the contexts of overexpressed SNHG1 and underexpressed miR-497-5p/miR-195-5p. Intriguingly, the strength of miR-195-5p collaborating with miR-497-5p in affecting the activity of CRC cells seemed to overweigh that of miR-497/miR-195-5p alone. Besides, both miR-195-5p and miR-497-5p were subjected to in vivo and in vitro modification of SNHG1 (p < .05). Conclusively, application of lncRNA SNHG1 for treating CRC might be promising, given its dual modulation of miR-497 and miR-195 underlying CRC pathogenesis.

Altered glucose metabolism has been found in a variety of malignant diseases and recognized as one of the hallmarks of cancer. However, the molecular mechanism behind it is far from well understood. In current study, we found silencer of death domains (SODD) regulates glucose uptake of colorectal cancer cells. When cultured under low level of glucose, SODD overexpressing RKO and SW1417 cells generated more colonies, compared with control cells, in clonogenic assay. SODD upregulation enhanced RKO and SW1417 cells viability. Furthermore, SODD induced more GLUT1 (Glucose transporter 1) expression and enhanced glucose uptake. AKT phosphorylation was upregulated in SODD overexpression cells. Moreover, inhibition of GLUT1 or AKT could reverse SODD induced glucose uptake enhancement. In conclusion, our findings indicate that SODD positively regulates glucose uptake and may be a potential therapeutic target of colorectal cancer.

MiR-30 family plays an important role in the tumorigenesis of human cancers. The aim of the study is to investigate the role of miR-30d in human colon cancer cell lines and explore the molecular mechanism in the proliferation of colon cancer cells. The expression of miR-30d was determined by real-time polymerase chain reaction assay in colon cancer cell lines (HCT15, HCT116, HT-29, DLD-1, and SW480) and the results demonstrated that miR-30d level was significantly decreased in human colon cancer cell lines, compared with normal colon epithelial cell line. Transfection with miR-30d mimics inhibited cell proliferation, and transfection with miR-30d inhibitors significantly promoted cell viability of colon cancer cells. Furthermore, TargetScan analysis predicted that miR-30d interacted with messenger RNA on its 3' untranslated region of ATG5, phosphoinositide 3-kinase, and Beclin1 to negatively regulate cell autophagy in colon cancer cells. Moreover, transfection with miR-30d induced cell arrest at G2/M phase of HT-29 cells. Overexpression of miR-30d mimics inhibited cell viability probably due to the inhibition of cell autophagy and promotion of cell apoptosis. Thus, MiR-30d inhibited cell autophagy by directly targeting messenger RNA of ATG5, phosphoinositide 3-kinase, and Beclin1 and promoted cell apoptosis of human colon cancer cells. It is helpful to clarify the function of miR-30d in tumorigenesis of human cancers.