Long non-coding RNA MCM3AP-AS1 promotes growth and migration through modulating FOXK1 by sponging miR-138-5p in pancreatic cancer

et al. 2020

Preprint

Background: Recently, accumulated numbers of studies have reported that long noncoding RNAs (lncRNAs) process an important role in tumorigenesis. As a new member found in lncRNAs, the role of lncRNA XIST (XIST) in colorectal cancer (CRC) was still elusive. The objective of this study was conducted to characterize a novel regulatory network involving XIST in CRC cells. Methods: The mRNAs of XIST, miR-497-5p, and forkhead box k1 (FOXK1) in CRC cells and tissues were detected using quantitative real-time polymerase chain reaction (qRT-PCR). And the proliferation and apoptosis of CRC cells were determined using cell counting kit-8 assay and flow cytometry. Moreover, we also detected the cell migration and invasion using Transwell assays. The relationships between XIST, miR-497-5p, and FOXK1 were predicted and then the dual-luciferase reporter assay was used to their relationships. The protein level of FOXK1 was quantitated using western blot. Results: In CRC tissues and cell lines, XIST expression was up-regulated, in which also existed miR-497-5p down-regulation and FOXK1 up-regulation. XIST knockdown suppressed CRC cell proliferation and migration as well as its invasion. Moreover, blocking the XIST expression could inhibit CRC tumor growth in vivo and the effects were antagonized by loss of miR-497-5p. miR-497-5p was identified as a sponge of XIST and also targeted FOXK1 in CRC cells. Besides, XIST silencing-mediated inhibitory activity against CRC progression reversed miR-497-5p down-regulation or FOXK1 up-regulation. Conclusion: In conclusion, XIST promotes the malignancy of colon cancer cells partly by competitively binding to miR-497-5p, which then led to increased FOXK1 expression. We conclude that targeting XIST may be a possible treatment for colon cancer.

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: The LncRNA XIST Promotes Colorectal Cancer Cell Growth Through Regulating miR-497-5p/FOXK1 Axis

Wang

et al. 2020

Preprint

“…Elevated expression of FOXK1 has been observed in breast cancer, and may contribute to pathogenesis by promoting cell proliferation and migration [19]. Increased FOXK1 expression has also been reported in gastric cancer tissues, as well as contributing to the invasion and metastasis of pancreatic cancer [20]. In this study, hsa-miR-497-5p was predicted to bind the 3'-UTR of FOXK1, resulting in weak expression of FOXK1 in colon cancer cells following upregulation of hsa-miR-497-5p.…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: The lncRNA XIST promotes colorectal cancer cell growth through regulating the miR-497-5p/FOXK1 axis

Wang

et al. 2020

Preprint

Background: Recent studies suggest that long noncoding RNAs (lncRNAs) play an important role in tumorigenesis. As a newly identified lncRNA, the role of XIST in colorectal cancer (CRC) has not been established. Here, we sought to characterize the role of XIST and its associated regulatory network in CRC cells.Methods: Expression of XIST mRNA, miR-497-5p, and forkhead box k1 (FOXK1) in CRC cells and tissues were detected using quantitative real-time polymerase chain reaction (qRT-PCR). Proliferation and apoptosis of CRC cells were determined using the CCK-8 cell counting assay and flow cytometry. The rate of cell migration and invasion was determined using a transwell assay. The relationships between XIST, miR-497-5p, and FOXK1 were predicted based on these results, and confirmed using a dual-luciferase reporter assay. Expression of FOXK1 protein was quantified by Western blot.Results: XIST and FOXK1 expression were significantly upregulated in CRC tissues and cell lines, while miR-497-5p expression was downregulated. XIST knockdown significantly suppressed CRC cell proliferation, migration, and invasion. Silencing of XIST also reversed the downregulation of miR-497-5p and upregulation of FOXK1. Moreover, blocking XIST expression was shown to inhibit CRC tumor growth in vivo and the effects were antagonized by the loss of miR-497-5p. miR-497-5p was shown to act as a sponge of XIST and also targeted FOXK1 in CRC cells.Conclusion: XIST was shown to promote the malignancy of CRC cells by competitively binding to miR-497-5p, resulting in an increase in FOXK1 expression. These results suggest that targeting of XIST may represent a possible treatment for colon cancer.

“…Overexpression of lncRNA MCM3AP-AS1 has been shown to promote proliferation, migration and invasion by sponging miR-138-5p in pancreatic cancer. 23 Similarly, our results demonstrated inhibitory effects of si-MCM3AP-AS1 on the proliferation, invasion, migration and the expression of SLC39A10 in PCa cells, and these effects could be reversed by 543-3p-inhibitor. In order to further confirm the role of lncRNA MCM3AP-AS1 in PCa cell behaviours, MCM3AP-AS1 was overexpressed and PCa cell proliferation, migration and invasion abilities were detected.…”

Section: Discussionsupporting

confidence: 74%

<p>LncRNA MCM3AP-AS1 Promotes Cell Proliferation and Invasion Through Regulating miR-543-3p/SLC39A10/PTEN Axis in Prostate Cancer</p>

Bian

et al. 2020

OTT

Objective: Long-chain noncoding RNAs (lncRNAs) are key players in a wide range of biological processes, especially the pathogenesis and development of tumors. LncRNA MCM3AP-AS1 has been demonstrated to be involved in the invasion of various tumors including prostate cancer (PCa). However, its functions in PCa have not been fully elucidated. Methods: qRT-PCR was conducted to measure the expression levels of lncRNA MCM3AP-AS1 and miR-543-3p in PCa tissue samples and cell lines. The expression levels of E-cadherin and SLC39A10 proteins were detected by Western blots. CCK-8 test, cell scratch test and trans-well test were used to evaluate the proliferation, invasion and migration abilities of PCa cells, respectively. Annexin V-FITC/PI experiments were carried out to determine the status of apoptosis. Bioinformatics analysis and Luciferase assay were used to explore the relationship between lncRNA MCM3AP-AS1, miR-543-3p and SLC39A10. Results: In PCa tissue samples and cell lines, lncRNA MCM3AP-AS1 was up-regulated while miR-543-3p was down-regulated. Over-expression of MCM3AP-AS1 could promote the proliferation and invasion of PCa cells. Correlation analysis showed that the expression of MCM3AP-AS1 and miR-543-3p was significantly and inversely correlated. We further verified that miR-543-3p inhibitor was able to reverse si-MCM3AP-AS1mediated inhibitory effects on the PCa cell proliferation, migration and invasion through regulating the downstream protein axis SLC39A10/PTEN/Akt. Finally, in vivo experiments indicated that knocking down of MCM3AP-AS1 could largely reduce tumor volumes, and decreased the ratio of Ki67-positive cells and the expression of SLC39A10 in tumor samples. Conclusion: LncRNA MCM3AP-AS1 can promote the proliferation, migration and invasion abilities of PCa cells through regulating the miR-543-3p/SLC39A10/PTEN axis, which suggests that lncRNA MCM3AP-AS1 might be a potential target for prostate cancer therapy.