Search

The present study aimed to evaluate the expression of human epidermal growth factor receptor (HER4) isoforms and their ligand neuregulin 1 (NRG1) isoforms in human primary colorectal cancer (CRC). The mRNA expression of HER4 isoforms JM-a, JM-b, CYT1 and CYT2, and their ligand isoforms NRG1 I, II and III in CRC tissues and adjacent normal tissues were quantified by reverse transcription-quantitative polymerase chain reaction analysis. Univariate analysis and logistic regression analysis were performed to analyze the association between HER4 and NRG1 expression and lymph node metastasis in CRC. The expression levels of CYT1 (P=0.002), CYT2 (P=0.002) and NRG1 type III (P<0.001) were significantly higher in the CRC tissues than in the adjacent normal tissues. The expression of CYT2 was correlated with tumor stage (P=0.018), lymph node status (P=0.015) and tumor-node-metastasis (P=0.038) in CRC. The expression of NRG1III was correlated with lymph node metastasis, and the expression of CYT2 was associated with the expression of NRG1III (r=0.691, P<0.01). The logistic regression analysis indicated that expression of CYT2 >50 was a risk factor for lymph node metastasis in CRC. In conclusion the expression levels of CYT1, CYT2 and NRG1III were upregulated in CRC. An expression of CYT-2 >50 was identified as a risk factor for lymph node metastasis in CRC. Therefore, CY-2 and NRG1III may be involved in the progression of CRC. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third most common cancer worldwide and its treatment remains a challenge. Effective control of cell survival and proliferation is critical in the prevention of oncogenesis and successful treatment of cancer. Long non-coding RNAs (lncRNAs) have emerged as primary regulators of carcinogenesis. Growth arrest specific 5 (GAS5), a lncRNA, is known to be aberrantly expressed in several types of cancer, however, the role of GAS5 in CRC remains unclear. In the present study, GAS5 mRNA expression was measured in CRC and adjacent normal mucosa tissue samples from 53 patients using reverse transcription-quantitative polymerase chain reaction analysis, in addition to seven CRC cell lines. GAS5 mRNA expression was observed to be markedly downregulated in human CRC tissues and cell lines. Decreased GAS5 expression was associated with an increase in tumor diameter [odds ratio (OR), 0.176 (95% CI, 0.053-0.586); P=0.003] and later tumor-node-metastasis stage [OR, 0.261 (95% CI, 0.083-0.819); P=0.019]. Patients with decreased GAS5 expression exhibited decreased overall survival rates compared with patients with increased GAS5 expression (P=0.015). The Cox proportional hazards model demonstrated that downregulated GAS5 expression was an independent prognostic factor for CRC (hazard ratio, 0.236; 95% confidence interval, 0.067-0.827; P=0.024). Functional assays demonstrated that overexpression of GAS5 inhibited cell proliferation and survival, and induced G0/G1 cell cycle arrest and apoptosis; however, knockdown of GAS5 expression enhanced cell proliferation, and reduced G0/G1 arrest and apoptosis. In conclusion, the results of the present study suggest that GAS5 is essential in the control of apoptosis and cell growth in CRC. Therefore, GAS5 may represent a novel prognostic and diagnostic marker of CRC, in addition to being a potential therapeutic target. [ABSTRACT FROM AUTHOR]