BACKGROUND Circular RNAs (circRNAs) are considered to be highly stable due to the closed structure, which are predominately correlated with the development and progression of a wide variety of cancers. Colon cancer is...BACKGROUND Circular RNAs (circRNAs) are considered to be highly stable due to the closed structure, which are predominately correlated with the development and progression of a wide variety of cancers. Colon cancer is one of the most common malignancies worldwide. A recent study demonstrated the upregulated expression of circPIP5K1A in non-small cell lung cancer. However, few studies have investigated the relationship between circ_0014130 level and colon cancer. Therefore, elucidating the underlying mechanisms of circPIP5K1A’s role may help with the identification of novel diagnostic and therapeutic targets for colon cancer. AIM To investigate the status of circPIP5K1A in colon cancers and its effects on the modulation of cancer development. METHODS The expression level of circPIP5K1A in tissue and serum samples from colon cancer patients, as well as human colonic cancer cell lines was detected by realtime quantitative reverse transcription-polymerase chain reaction. Following the transfection of specifically synthesized small interfering RNA (siRNA) into colon cell lines, we used Hoechst staining assay to measure the ratio of cell death in the absence of circPIP5K1A. Moreover, we also used the Transwell assay to assess the migratory function of colon cells overexpressing circPIP5K1A. Additionally, we employed a series of bioinformatics prediction programs to predict the potential of circPIP5K1A-targeted miRNAs and mRNAs. The miR-1273a vector was constructed, and then transfected with or without circPIP5K1A vector into colon cancer cells. Afterwards, the expression of activator protein 1 (AP-1), interferon regulating factor 4 (IRF-4), caudal type homeobox 2 (CDX-2), and zinc finger of the cerebellum 1 (Zic-1) was detected by western blotting. RESULTS CircPIP5K1A was significantly upregulated in colon cancer tissue relative to their adjacent normal tissues. Knockdown of circPIP5K1A in colon cancer cells impaired cell viability and suppressed cell invasion and migration, while enforced expression of circPIP5K1A exhibited the opposite effects on cell migration. Bioinformatics prediction program predicted that the association of circPIP5K1A with miR-1273a, as well as AP-1, IRF-4, CDX-2, and Zic-1. Subsequent studies showed that overexpression of circPIP5K1A augmented the expression of AP-1 but attenuated the expression of IRF-4, CDX-2, and Zic-1. Reciprocally, overexpression of miR-1273a abrogated the oncogenic function of circPIP5K1A in colon cancers. CONCLUSION Overall, our data demonstrate the oncogenic role of circPIP5K1A-miR-1273a axis in regulation of colon cancer development, which provides a novel insights into colon cancer pathogenesis.展开更多
基金Supported by the National Natural Science Foundation of China,No.81703028and Hubei Cancer Hospital,No.20162017B01
文摘BACKGROUND Circular RNAs (circRNAs) are considered to be highly stable due to the closed structure, which are predominately correlated with the development and progression of a wide variety of cancers. Colon cancer is one of the most common malignancies worldwide. A recent study demonstrated the upregulated expression of circPIP5K1A in non-small cell lung cancer. However, few studies have investigated the relationship between circ_0014130 level and colon cancer. Therefore, elucidating the underlying mechanisms of circPIP5K1A’s role may help with the identification of novel diagnostic and therapeutic targets for colon cancer. AIM To investigate the status of circPIP5K1A in colon cancers and its effects on the modulation of cancer development. METHODS The expression level of circPIP5K1A in tissue and serum samples from colon cancer patients, as well as human colonic cancer cell lines was detected by realtime quantitative reverse transcription-polymerase chain reaction. Following the transfection of specifically synthesized small interfering RNA (siRNA) into colon cell lines, we used Hoechst staining assay to measure the ratio of cell death in the absence of circPIP5K1A. Moreover, we also used the Transwell assay to assess the migratory function of colon cells overexpressing circPIP5K1A. Additionally, we employed a series of bioinformatics prediction programs to predict the potential of circPIP5K1A-targeted miRNAs and mRNAs. The miR-1273a vector was constructed, and then transfected with or without circPIP5K1A vector into colon cancer cells. Afterwards, the expression of activator protein 1 (AP-1), interferon regulating factor 4 (IRF-4), caudal type homeobox 2 (CDX-2), and zinc finger of the cerebellum 1 (Zic-1) was detected by western blotting. RESULTS CircPIP5K1A was significantly upregulated in colon cancer tissue relative to their adjacent normal tissues. Knockdown of circPIP5K1A in colon cancer cells impaired cell viability and suppressed cell invasion and migration, while enforced expression of circPIP5K1A exhibited the opposite effects on cell migration. Bioinformatics prediction program predicted that the association of circPIP5K1A with miR-1273a, as well as AP-1, IRF-4, CDX-2, and Zic-1. Subsequent studies showed that overexpression of circPIP5K1A augmented the expression of AP-1 but attenuated the expression of IRF-4, CDX-2, and Zic-1. Reciprocally, overexpression of miR-1273a abrogated the oncogenic function of circPIP5K1A in colon cancers. CONCLUSION Overall, our data demonstrate the oncogenic role of circPIP5K1A-miR-1273a axis in regulation of colon cancer development, which provides a novel insights into colon cancer pathogenesis.
