IDDF2019-ABS-0246 LncRNA XIST regulated chemotherapeutic sensitivity of mir-125b-2–3p by targeting wee1 in colorectal cancer

Abstract 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 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. Conclusions 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 CRC.

Download Full-text

LncRNA XIST modulates HIF‐1A/AXL signaling pathway by inhibiting miR‐93‐5p in colorectal cancer

Molecular Genetics & Genomic Medicine ◽

10.1002/mgg3.1112 ◽

2020 ◽

Vol 8 (4) ◽

Cited By ~ 2

Author(s):

Li‐guang Yang ◽

Ming‐zheng Cao ◽

Jie Zhang ◽

Xiao‐yan Li ◽

Qin‐li Sun

Keyword(s):

Colorectal Cancer ◽

Signaling Pathway ◽

Lncrna Xist

Download Full-text

miR-204-5p Inhibits Proliferation and Invasion and Enhances Chemotherapeutic Sensitivity of Colorectal Cancer Cells by Downregulating RAB22A

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-14-1030 ◽

2014 ◽

Vol 20 (23) ◽

pp. 6187-6199 ◽

Cited By ~ 108

Author(s):

Yuan Yin ◽

Binbin Zhang ◽

Weili Wang ◽

Bojian Fei ◽

Chao Quan ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Chemotherapeutic Sensitivity ◽

Colorectal Cancer Cells ◽

Proliferation And Invasion

Download Full-text

Astragaloside IV Induced miR-134 Expression Reduces EMT and Increases Chemotherapeutic Sensitivity by Suppressing CREB1 Signaling in Colorectal Cancer Cell Line SW-480

Cellular Physiology and Biochemistry ◽

10.1159/000482025 ◽

2017 ◽

Vol 43 (4) ◽

pp. 1617-1626 ◽

Cited By ~ 18

Author(s):

Qi Ye ◽

Li Su ◽

Dagui Chen ◽

Wenyi Zheng ◽

Ye Liu

Keyword(s):

Colorectal Cancer ◽

Drug Resistance ◽

Cell Migration ◽

Luciferase Reporter ◽

Colorectal Cancer Cell Line ◽

Migration And Invasion ◽

Astragaloside Iv ◽

Mesenchymal Transition ◽

Cell Migration And Invasion ◽

Chemotherapeutic Sensitivity

Background: Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Although chemotherapy is the primary means in colorectal cancer treatment, it is burdenerd by adverse drug effects. Drug-resistance is one of the most important challenges for chemotherapy and epithelial-mesenchymal transition (EMT) plays critical role in the development of drug resistance. Aims: The aim of this study was to investigate the mechanisms underlying the effect of astragaloside IV (AS-IV) on miR-134 expression, EMT and chemotherapeutic sensitivity in CRC. Methods: Cell proliferation, transfection assay, western blot, real-time PCR, cell migration and invasion assay and luciferase reporter assay were used to detect the effects of AS-IV on CRC. Results: AS-IV significantly inhibited CRC cell migration and invasion by inducing miR-134 expression. Moreover, AS-IV and miR-134 increased the sensitivity of CRC tumors to oxaliplatin (OXA) chemotherapy. cAMP responsive element-binding protein 1 (CREB1), which was required for CRC cells migration, invasion and drug sensitivity, was significantly down-regulated by AS-IV. Conclusions: Our results indicated that AS-IV inhibited CRC EMT by inducing miR-134 expression which significantly down-regulated the CREB1 signaling pathway, and therefore increased the sensitivity to chemotherapy. Our findings provided new insight into the mechanisms of chemotherapy-resistant CRC, and may open new therapeutic options in the treatment of this devastating disease.

Download Full-text

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

10.21203/rs.3.rs-36553/v1 ◽

2020 ◽

Author(s):

Nan Wang ◽

Jia-Xing He ◽

Guo-Zhan Jia ◽

Ke Wang ◽

Shuai Zhou ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Cell Counting ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Xist Expression ◽

Cancer Cell Growth ◽

Down Regulation ◽

Lncrna Xist ◽

And Migration

Abstract 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.

Download Full-text