Abstract
Micro RNAs (miRNAs) are important regulators involved in various physical and pathological processes, including cancer. The miRNA-302 family has been documented as playing a critical role in carcinogenesis. In this study, we investigated the role of miRNA-302a in colon cancer. MiRNA-302a expression was detected in 44 colon cancer tissues and 10 normal colon tissues, and their clinicopathological significance was analyzed. Cell proliferation and cell cycle analysis were performed on colon cancer cells that stably expressed miRNA-302a. The target gene of miRNA-302a and the downstream pathway were further investigated. Compared with normal colon tissues, miRNA-302a expression was downregulated in colon cancer tissues. Overexpression of miRNA-302a induced G1/S cell cycle arrest in colon cancer cells, and suppressed colon cancer cell proliferation both in vitro and in vivo. Furthermore, miRNA-302a inhibited AKT expression by directly binding to its 3′ untranslated region, resulting in subsequent alterations of the AKT-GSK3β-cyclin D1 pathway. These results reveal miRNA-302a as a tumor suppressor in colon cancer, suggesting that miRNA-302a may be used as a potential target for therapeutic intervention in colon cancer.
Highlights
According to the Chinese Cancer Registry Annual Report (2012), colon/rectal cancer has become the second most common cancer and the second and fourth leading cause of cancer-related mortality in women and men, respectively, in China [1]
MiRNA-302a expression is suppressed in colon cancer tissues
Given the critical role of the AKT-GSK3b-cyclin D1 signaling pathway in cell cycle transition, our results suggest that Micro RNAs (miRNAs)-302a might induce G1/S cell cycle arrest in colon cancer cells by inhibiting the AKT-GSK3b-cyclin D1 pathway, thereby suppressing colon cancer cell proliferation
Summary
According to the Chinese Cancer Registry Annual Report (2012), colon/rectal cancer has become the second most common cancer and the second and fourth leading cause of cancer-related mortality in women and men, respectively, in China [1]. Colon cancer is one of the most common cancers globally, accounting for approximately 9% of cancer related deaths [2], mostly due to metastatic progression [3]. Surgery remains the therapy of choice for colon cancer; but of late, a more multidisciplinary approach incorporating neoadjuvant chemotherapy has become the hallmark of treatment [4] It perhaps cannot be emphasized enough though the need to monitor the tumor response to therapy in order for selecting the best candidates for surgery to ensure positive outcomes, and there lies the need to understand the underlying pathologic mechanism of colon cancer onset and progression. The critical events that control the whole process of colon cancer metastasis are still largely unknown
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