C Du1, H-X Wang, P Chen, C-H Chen. 1. Department of Gastroenterology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, China. ducc77416@163.com.
Abstract
OBJECTIVE: Previous reports have shown that long non-coding RNAs (lncRNAs) are involved in a series of biological processes and cancer in humans. Recently, lncRNA double homeobox A pseudogene 8 (DUXAP8) was frequently reported to be aberrantly expressed in multiple cancers and play a functional role. However, the exact expression, function, and mechanism of DUXAP8 in colorectal cancer (CRC) remain uncovered. PATIENTS AND METHODS: The expression levels of DUXAP8 were detected by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). The clinical influence of DUXAP8 in HCC patients was statistically analyzed. Luciferase reporter and ChIP assays were carried out for the exploration of whether STAT3 was able to bind to the promoter of DUXAP8. Lost-of-function experiments were carried out for the determination of possible cellular function in CRC cells. The modulating associations between DUXAP8 and miR-577 and RAB14 were further studied in CRC cells. RESULTS: In this study, we first provided evidence that DUXAP8 was overexpressed in CRC and increasing expression of DUXAP8 indicates advanced clinical progression and poor survival of CRC patients. Then, transcription factor STAT3 was demonstrated to upregulate DUXAP8 in CRC cells. Functional assays via in vitro assays revealed that DUXAP8 knockdown through shRNA in HCT116 and LOVO cells inhibited cell proliferation, migration and invasion, and promoted apoptosis. Furthermore, an inverse relationship between DUXAP8 and miR-577 was found. In addition, we confirmed that DUXAP8 served as competing endogenous RNA to modulate miR-577, which can modulate RAB14, a well-studied oncogene. CONCLUSIONS: Our study revealed that the STAT3-induced up-regulation of DUXAP8 might provide a new perspective for CRC therapy.
OBJECTIVE: Previous reports have shown that long non-coding RNAs (lncRNAs) are involved in a series of biological processes and cancer in humans. Recently, lncRNA double homeobox A pseudogene 8 (DUXAP8) was frequently reported to be aberrantly expressed in multiple cancers and play a functional role. However, the exact expression, function, and mechanism of DUXAP8 in colorectal cancer (CRC) remain uncovered. PATIENTS AND METHODS: The expression levels of DUXAP8 were detected by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). The clinical influence of DUXAP8 in HCCpatients was statistically analyzed. Luciferase reporter and ChIP assays were carried out for the exploration of whether STAT3 was able to bind to the promoter of DUXAP8. Lost-of-function experiments were carried out for the determination of possible cellular function in CRC cells. The modulating associations between DUXAP8 and miR-577 and RAB14 were further studied in CRC cells. RESULTS: In this study, we first provided evidence that DUXAP8 was overexpressed in CRC and increasing expression of DUXAP8 indicates advanced clinical progression and poor survival of CRC patients. Then, transcription factor STAT3 was demonstrated to upregulate DUXAP8 in CRC cells. Functional assays via in vitro assays revealed that DUXAP8 knockdown through shRNA in HCT116 and LOVO cells inhibited cell proliferation, migration and invasion, and promoted apoptosis. Furthermore, an inverse relationship between DUXAP8 and miR-577 was found. In addition, we confirmed that DUXAP8 served as competing endogenous RNA to modulate miR-577, which can modulate RAB14, a well-studied oncogene. CONCLUSIONS: Our study revealed that the STAT3-induced up-regulation of DUXAP8 might provide a new perspective for CRC therapy.
Authors: Teng Li; Yi Xing; Fan Yang; Yangyang Sun; Shaojin Zhang; Qingwei Wang; Weixing Zhang Journal: Cancer Med Date: 2020-04-05 Impact factor: 4.452