MiR-1297 Regulates the Growth, Migration and Invasion of Colorectal Cancer Cells by Targeting Cyclo-oxygenase-2

Abstract

Asian Pac J Cancer Prev, 15 (21), 9185-9190 IntroductionColorectal cancer (CRC) is one of the most common malignant tumors of the gastrointestinal tract. With an estimated 140 thousand new cases and over 50 thousand deaths in 2013, colorectal cancer (CRC) is the fourth most common cancer that leads to mortality in the United States (Committee et al., 2013). In addition, the incidence and mortality of colorectal cancer has continued to rise rapidly in China over the past few decades. The incidence of CRC has increased by an annual average of 5.73% from 1992 to 2005 (13.06 to 23.54/100000) in the Nangang District of Harbin, China (Hu et al., 2013). Though the exact mechanism of CRC is still unknown, it has been well established that smoking, obesity, red meat consumption, excessive alcohol consumption, and chronic intestinal inflammation are risk factors for CRC; (Wang et al., 2010;Theodoratou et al., 2012;Burn et al., 2013). Of these risk factors, chronic intestinal inflammation has been considered one of the most significant causes of colon cancer (Wang and Dubois, 2010).Many studies have confirmed the relationship of cyclooxygenase-2 (Cox-2) and the CRC development and progression leading to chronic inflammation (Williams et al., 1999). Cox-2 is an early inflammation response gene, previously shown to be up-regulated in 40-50% of colorectal adenomas and 85% of CRC, leading to AbstractCyclo-oxygenase-2(Cox-2), a key regulator of inflammation-producing prostaglandins, promotes cell proliferation and growth. Therefore, a better understanding of the regulatory mechanisms of Cox-2 could lead to novel targeted cancer therapies. MicroRNAs are strongly implicated in colorectal cancer but their specific roles and functions have yet to be fully elucidated. MiR-1297 plays an important role in lung adenocarcinoma and laryngeal squamous cell carcinoma, but its significance in colorectal cancer (CRC) has yet to be reported. In our present study, we found miR-1297 to be down regulated in both CRC-derived cell lines and clinical CRC samples, when compared with normal tissues. Furthermore, miR-1297 could inhibit human colorectal cancer LOVO and HCT116 cell proliferation, migration, and invasion in vitro and tumorigenesis in vivo by targeting Cox-2. Moreover, miR-1297 directly binds to the 3`-UTR of Cox-2, and the expression level was drastically decreased in LOVO and HCT116 cells following overexpression of miR-1297. Additionally, Cox-2 expression levels are inversely correlated with miR-1297 expression in human colorectal cancer xenograft tissues. These results imply that miR-1297 has the potential to provide a new approach to colorectal cancer therapy by directly inhibiting Cox-2 expression.

MicroRNA-101 inhibits proliferation, migration and invasion of human glioblastoma by targeting SOX9

“…The miRNAs are kind of endogenous non - coding RNA, they can negatively regulate the target genes expression on post - transcriptional level through binding to the 3′UTR of their mRNA [33]. The deregulation of miRNAs had been found in many human cancers, such as ovarian carcinoma [34], lung cancer [35,36], liver cancer [37], colon cancer [38, 39] and GBM [40]. MiRNA deregulation has become a new characteristic of malignant tumor, so some specific miRNAs are potentially novel biomarkers of cancer diagnosis and prognosis [41–45].…”

Correlation between miR‐21 expression and laryngeal carcinoma risks: a meta‐analysis

“…Recent studies have demonstrated that miR-21 can regulate some important oncogenes or suppressor genes such as vascular endothelial growth factor (VEGF), phosphatase and tensin homolog (PTEN), etc. Therefore, higher expression of miR-21 in tumor tissue might indicate more aggressive of the tumor, such as colorectal cancer, breast cancer, gastric cancer, and liver cancer (19,(22)(23)(24)(25)(26).…”

MicroRNA-1297 inhibits metastasis and epithelial-mesenchymal transition by targeting AEG-1 in cervical cancer

“…However, miR-1297 inhibited prostate cancer cell proliferation and invasion by targeting the AEG-1/Wnt signaling pathway (18). miR-1297 inhibited the growth, migration and invasion of colorectal cancer cells by targeting cyclo-oxygenase-2 (19). These studies revealed that miR-1297 was a tumor suppressor.…”