Search

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.

IntroductionRecent studies have proved the diverse roles of miRs in different cancer-related processes. This study was undertaken to determine the therapeutic implications of miR-325-3p in breast cancer.Material and methodsExpression analysis was carried out by qRT-PCR. Transfections were performed by Lipofectamine 2000 reagent. MTT assay was used for cell viability. Transwell assays were used for cell migration and invasion. Western blot analysis was used for protein expression analysis.ResultsGene expression analysis revealed miR-325 to be significantly suppressed in breast cancer tissues and cell lines. Nonetheless, ectopic expression of miR-325 resulted in suppression of the growth and colony development potential of the SK-BR-3 and CAMA-1 cells. Transwell assays showed that miR-325 overexpression also resulted in the decline of the migration and invasion of the SK-BR-3 and CAMA-1 cells. Bioinformatic analysis showed that miR-325 targets lipocalin 15 (LNC15) in breast cancer cells. LNC15 was also overexpressed in the breast cancer tissues and cell lines. However, overexpression of miR-325 caused a significant decline in the LNC15 expression in SK-BR-3 cells. Additionally, silencing of LNC15 resulted in inhibition of the growth, migration and invasion of the SK-BR-3 cells. Rescue assay showed that overexpression of LNC15 could promote the growth, migration and invasion of the miR-325 overexpressing effects.ConclusionsTaken together, the evidence shows that miR-325 acts as a tumor suppressor in breast cancer and may be used in the treatment of breast cancer.

// 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.

A hybrid drug delivery system (DDS) composed of hyaluronan and calcium carbonate (CC) was developed. By taking advantage of the tumor-targeting ability of hyaluronan and the drug-loading property of CC, the well-formed hyaluronan–CC nanoparticles were able to serve as a DDS targeting colorectal cancer with a decent drug loading content, which is beneficial in the chemotherapy of colorectal cancer. In this study, hyaluronan–CC nanoparticles smaller than 100 nm were successfully developed to load the wide-range anti-cancer drug adriamycin (Adr) to construct hyaluronan–CC/Adr nanoparticles. On the other hand, we also found that hyaluronan–CC/Adr nanoparticles can possibly increase the uptake ratio of Adr into HT29 colorectal cancer cells when compared with hyaluronan-free nanoparticles (CC/Adr) via the CD44 receptor-mediated endocytosis via competitive uptake and in vivo imaging assays. Note that both in vitro (CCK-8 assay on HT29 cells) and in vivo (anti-cancer assay on HT-29 tumor-bearing nude mice model) experiments revealed that hyaluronan–CC/Adr nanoparticles exhibited stronger anti-cancer activity than free Adr or CC/Adr nanoparticles with minimized toxic side effects and preferable cancer-suppression potential.