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Background: LncRNAs are involved in the metastasis and recurrence of human tumors, including colorectal cancer (CRC). We previously reported that lncRNA AB073614 promotes tumor proliferation and metastasis and predicted a poor clinical outcome of CRC patients. Herein, we investigated the underlying mechanism of lncRNA AB073614-related metastasis in CRC., Material and Methods: The expression of lncRNA AB073614 in CRC tissues were evaluated by quantitative real-time PCR (qRT-PCR). Transwell assay was performed to detect the effects of lncRNA AB073614 on cell migration and invasion. Epithelial-mesenchymal transition (EMT) molecular markers and Janus kinase/signal transducer and activator of transcription (JAK/STAT3) pathway proteins expression levels were detected by Western blot and Immunofluorescence., Results: We confirmed that lncRNA AB073614 was highly expressed in the colorectal cancer tissues. LncRNA AB073614 knockdown in SW480 and HCT116 cells significantly promoted the protein expression levels of E-cadherin and Occludin, and decreased the expressions of N-cadherin and Vimentin, then further decreased the cell migration and invasion ability. Interestingly, the expression of phosphorylated STAT3 was also down-regulated. Furthermore, SW480 and HCT116 cells were transfected with lncRNA AB073614 vector and treated with a JAK inhibitor, AT9283. The results showed that lncRNA AB073614 regulated EMT through JAK-STAT3 signaling pathway., Conclusion: All these results indicate that lncRNA AB073614 can induce the expression of EMT cell markers and regulate the process of EMT of CRC cells through regulating the JAK/STAT3 pathway activation.

microRNAs (miR) can potentially be used for categorizing the various subtypes of colorectal cancer (CRC) and predicting a patient's response to treatment with traditional anti-CRC therapies. We investigated how miR-1297 and its potential target molecule cyclin D2 (CCND2) might affect the progression of CRC. Thirty-two pairs of CRC specimens and corresponding samples of para-tumor tissue were collected and examined for their levels of miR-1297 and CCND2 expression. We also examined miR-1297 and CCND2 expression in cultured SW480 cells. The effects of modulated levels of miR-1297 and CCND2 on cell viability, anchorage-independent growth ability, proliferation, apoptosis, cell cycle distribution, migration, and invasion were detected using specific techniques. The possible regulatory effect of miR-1297 on CCND2 was investigated using dual luciferase assays. Our results showed that miR-1297 expression was downregulated in clinical CRC specimens, and such downregulation was associated with upregulated levels of CCND2 expression. Upregulation of miR-1297 and downregulation of CCND2 reduced the proliferation and metastasis potential of SW480 cells, but did not affect the apoptotic process. In addition, miR-1297 regulated CCND2 function by directly binding to the promoter sequence of the CCND2 gene, which would block CCND2-related signaling at the transcription level. Our findings validate the anti-CRC function of miR-1297 and pro-CRC function of CCND2. Our findings may assist in developing miR-based therapies against CRC.

The expression profiles of long noncoding RNAs (lncRNAs) in colorectal cancer (CRC) have remained unclear. LncRNA AB073614 is known to be upregulated in ovarian cancer and glioma tissues, and is associated with the occurrence and progression of those cancers. In the present study, we investigated the lncRNA AB073614 gene expression patterns in CRC cell lines and tissue samples from CRC patients, and then analyzed them for possible associations with various clinicopathological characteristics. Furthermore, the roles played by lncRNA AB073614 in CRC cell proliferation, apoptosis, cell cycle progression, migration, and invasion were examined in vitro by using gene knockdown and overexpression techniques. We detected the levels of lncRNA AB073614 in 28 paired CRC tissues and adjacent normal tissues by qRT-PCR, and our results revealed that AB073614 expression in 85.7% (24/28) of the CRC tissues was significantly higher than those in the paired normal tissues. Furthermore, the levels of AB073614 were closely related to tumor grade, size, cell differentiation status, and the presence of distant metastases. Knockdown of AB073614 expression significantly inhibited the proliferation, migration, and invasion of SW480 cells, and resulted in their increased rates of apoptosis and G1 phase cell cycle arrest, whereas overexpression of AB073614 produced the opposite effects. Finally, results of studies which used an agonist (740Y-P) and an inhibitor (LY294002) of the PI3K/AKT signaling pathway, as well as the results of western blot assays, indicated that lncRNA AB073614 exerts its effects by targeting the PI3K/AKT-mediated signaling pathway. Taken together, our data indicate that lncRNA AB073614 acts to prevent CRC progression by affecting the PI3K/AKT signaling pathway, and may be useful as a novel prognostic or treatment agent for CRC., (Copyright © 2017. Published by Elsevier Masson SAS.)