Expression of inositol-requiring enzyme 1β is downregulated in colorectal cancer

The endoplasmic reticulum stress inositol-requiring enzyme (IRE) 1 alpha/X-box binding protein (XBP) 1 signaling pathway is involved in the tumorigenesis of breast and prostate cancer. Mucin 2 (MUC2) protects colon tissues from the formation of tumors. In human colorectal cancer (CRC) the role of IRE1 alpha, and its analogue, IRE1 beta, has yet to be elucidated. In the present study, the expression levels of IRE1a, IRE1 alpha, un-spliced XBP1u, spliced XBP1s and MUC2 in surgically resected cancerous and adjacent non-cancerous tissues from patients with CRC were investigated. The IRE1a, IRE1 beta, XBP1u, XBP1s and MUC2 mRNA expression levels were determined using reverse transcription-quantitative polymerase chain reaction, and the protein expression levels were detected using immunohistochemistry and western blotting. The association between the expression levels of IRE1 alpha, IRE1 beta and MUC2 and the clinicopathological features of patients with CRC was subsequently analyzed. The mRNA expression levels of IRE1 beta and MUC2 were decreased by similar to 2.1 and similar to 4.5-fold in CRC tissues, respectively, as compared with the adjacent normal tissues. The protein expression levels of IRE1 beta and MUC2 were decreased by similar to 8.0 and similar to 2.0-fold in the CRC tissues, respectively. IRE1 beta mRNA expression levels were positively correlated with MUC2 mRNA expression levels. IRE1 beta expression levels were revealed to be significantly associated with lymph node metastasis, tumor stage and histological differentiation. However, IRE1a, XBP1u and XBP1s mRNA and IRE1a protein expression levels were not observed to significantly differ between cancerous tissues and the adjacent normal tissues. The results indicated that the expression of IRE1 beta, but not IRE1 alpha, may protect colon tissue from developing CRC by inducing MUC2 expression. Therefore, decreased IRE1 beta expression levels may be associated with the development of CRC through the inhibition of MUC2 expression.