CircCSPP1 Functions as a ceRNA to Promote Colorectal Carcinoma Cell EMT and Liver Metastasis by Upregulating COL1A1.

The aberrant regulation of circular RNAs (circRNAs), ring structures formed by exon or intron backsplicing, has been identified as a novel characteristic of multiple cancers. However, the role of circRNAs in colorectal carcinoma remains to be elucidated. In the present study, we investigated the mRNA level and the promoting effect of circRNA CSPP1 (circCSPP1) in colorectal carcinoma liver metastasis. By bioinformatic analysis of 10 paired samples of colorectal carcinoma and adjacent mucosal tissues, we identified circCSPP1 as a significantly upregulated circRNA in colorectal carcinoma tissues, and its upregulation was correlated with a higher M stage. The gain- and loss-of-function assays revealed that circCSPP1 promotes the migration and invasion of colorectal carcinoma cells in vitro and in vivo. Mechanistically, similar miRNA response elements are shared between circCSPP1 and COL1A1. We demonstrated that circCSPP1 upregulates the mRNA levels of COL1A1, which plays a pivotal role in the process of epithelial-mesenchymal transition (EMT), by competitively binding to miR-193a-5p and preventing miR-193a-5p from decreasing the expression of COL1A1. In conclusion, this finding indicates that circCSPP1 may act as a promising therapeutic target by regulating the EMT process in colorectal carcinoma via activation of the circCSPP1/miR-193a-5p/COL1A1 axis.

Downregulation of long noncoding RNA SNHG1 inhibits cell proliferation, metastasis, and invasion by suppressing the Notch-1 signaling pathway in pancreatic cancer.

BACKGROUND: Pancreatic cancer (PC) has become the fourth most lethal among human cancers. Long noncoding RNAs (lncRNAs) have been reported to play a role in the progression of a variety of cancers. However, the role of lncRNA SNHG1 in PC is not clear. METHODS: Real-time Quantitative PCR Detection System (qPCR) was used to detect the expression of SNHG1 in PC cells. Then, the SNHG1 knockdown cell was constructed with si-SNHG1. AsPC-1 and PANC1 cells were used to analyze the ability of cell proliferation, invasion, and migration. MTT assay was used to analyze the proliferation ability. Transwell experiments and wound healing experiments were used to detect the capacity of invasion and migration. Finally, Western blot analysis was used to explore the mechanism of SNHG1 in PC. RESULTS: SNHG1 was significantly upregulated in PC cells. Knockdown of SNHG1 could obviously suppress cell proliferation, invasion, and migration. Furthermore, SNHG1 knockdown inhibited the activation of the Notch-1 signaling pathway and inhibited the expression of N-cadherin, Hes1, Vimentin, Notch-1. The inhabitation was reversed when Notch-1 was overexpressed in si-SNHG1 cells. CONCLUSION: The lncRNA SNHG1 promotes cell growth and metastasis in PC through activation of the Notch-1 signaling pathway in PC.

The autophagy-related genes Beclin1 and LC3 in the prognosis of pancreatic cancer.

PURPOSE: To investigate the role of the autophagy-related genes Beclin1 and LC3 in the prognosis of pancreatic cancer. METHODS: A total of 86 pancreatic cancer tissues and 84 paired, adjacent normal pancreatic tissues were collected from 86 patients who underwent pancreatic resection surgery in our hospital from January 2009 to August 2011. Demographic data including age, gender, family cancer history, and clinic-pathological characteristics, including tumor diameter, differential, TNM staging and lymphatic metastasis were collected. The expressions of Beclin1 and LC3 were determined using both immunohistochemistry (IHC) and RT-qPCR. RESULTS: The expression levels of both Beclin1 and LC3 mRNA and proteins were significantly up-regulated in the tumor tissues compared with the normal tissues. Higher expressions of Beclin1 and LC3 were found in the tumor tissues of patients with TNM stages III~IV, patients with lymphatic metastasis, and patients who died. Meanwhile Beclin1 and LC3 correlated with TNM stage, differential condition, and the patients' lymphatic metastasis rates. A survival analysis showed that patients with low expressions of Beclin1 and LC3 had longer survival times, and both the Beclin1 and LC3 genes were independent risk factors for 5-year mortality in pancreatic cancer patients. CONCLUSION: The Beclin1 and LC3 genes correlate with the tumor stage, metastasis conditions, and pancreatic cancer patients' mortality.

Zinc protoporphyrin IX enhances chemotherapeutic response of hepatoma cells to cisplatin.

AIM: To investigate the effect of zinc protoporphyrin IX on the response of hepatoma cells to cisplatin and the possible mechanism involved. METHODS: Cytotoxicity was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis was determined by a flow cytometric assay. Western blotting was used to measure protein expression. Heme oxygenase (HO)-1 activity was measured by determining the level of bilirubin generated in isolated microsomes. Reactive oxygen species (ROS) production was monitored by flow cytometry. Caspase-3 activity was measured with a colorimetric assay kit. Mice were inoculated with 1 × 10(7) tumor cells subcutaneously into the right flanks. All mice were sacrificed 6 wk after the first treatment and tumors were weighed and measured. RESULTS: Overexpression of HO-1 in HepG2 cell line was associated with increased chemoresistance to cis-diaminedichloroplatinum (cisplatin; CDDP) compared to other cell lines in vitro. Inhibition of HO-1 expression or activity by zinc protoporphyrin IX (ZnPP IX) markedly augmented CDDP-mediated cytotoxicity towards all liver cancer cell lines in vitro and in vivo. In contrast, induction of HO-1 with hemin increased resistance of tumor cells to CDDP-mediated cytotoxicity in vitro and in vivo. Furthermore, cells treated with ZnPP IX plus CDDP exhibited marked production of intracellular ROS and caspase-3 activity, which paralleled the incidence of cell apoptosis, whereas hemin decreased cellular ROS and caspase-3 activity induced by CDDP. CONCLUSION: ZnPP IX increases cellular sensitivity and susceptibility of liver cancer cell lines to CDDP and this may represent a mechanism of increasing ROS.