Long noncoding RNA MALAT1 mediates stem cell‐like properties in human colorectal cancer cells by regulating miR‐20b‐5p/Oct4 axis

Cancer stem cells (CSCs) are crucial components of the tumor microenvironment that take part in tumor initiation, progression, recurrence, metastasis, and resistance to chemotherapy. This study explores the mechanisms through which CSCs maintain their stemness, especially in tumors of colorectal can...

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Veröffentlicht in:Journal of cellular physiology 2019-11, Vol.234 (11), p.20816-20828
Hauptverfasser: Tang, Dongxin, Yang, Zhu, Long, Fengxi, Luo, Li, Yang, Bing, Zhu, Ruyi, Sang, Xianan, Cao, Gang, Wang, Kuilong
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container_end_page 20828
container_issue 11
container_start_page 20816
container_title Journal of cellular physiology
container_volume 234
creator Tang, Dongxin
Yang, Zhu
Long, Fengxi
Luo, Li
Yang, Bing
Zhu, Ruyi
Sang, Xianan
Cao, Gang
Wang, Kuilong
description Cancer stem cells (CSCs) are crucial components of the tumor microenvironment that take part in tumor initiation, progression, recurrence, metastasis, and resistance to chemotherapy. This study explores the mechanisms through which CSCs maintain their stemness, especially in tumors of colorectal cancer (CRC), which thus far remain uncertain. Our findings indicated that the expression of miR‐20b‐5p is negatively correlated with that of metastasis‐associated lung adenocarcinoma transcript‐1 (MALAT1, r = −0.928, p = 0.023) and Oct4 (r = −0.894, p = 0.041) in CRC cells. We hypothesized that there may be some targeted regulatory relationships among MALAT1, miR‐20b‐5p, and Oct4. We proceeded to show that both si‐MALAT1 and miR‐20b‐5p‐mimic attenuated microsphere formation and self‐renewal capacity, decreased the proportion of CSCs, and downregulated the expression of proteins associated with tumor cell stemness maintenance (Oct4, Nanog, sex‐determining region Y‐box 2, and Notch1) and cellular metabolism (glucose transporter 1, lactate dehydrogenase B, hexokinase 2, and pyruvate kinase isozyme M2) in HCT‐116 cells in vitro. In addition, a xenograft model based on Balb/c mice demonstrated that the administration of either si‐MALAT1 or miR‐20b‐5p‐mimic suppressed the tumorigenicity of HCT‐116 cells in vivo. The underlying mechanisms may involve the targeting of the tumor cell stemness maintenance‐related factor Oct4 by miR‐20b‐5p. For the first time, we present the possible underlying effects of MALAT1 in influencing the stem cell‐like properties of CRC cells. We propose that microRNAs and long noncoding RNAs have vital functions in mediating tumor stemness, which remain to be fully elucidated. We present the possible underlying effects of MALAT1 in influencing the stem cell‐like properties of colorectal cancer cells. We propose that microRNAs and long noncoding RNAs have vital functions in mediating tumor stemness, which remain to be fully elucidated.
doi_str_mv 10.1002/jcp.28687
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This study explores the mechanisms through which CSCs maintain their stemness, especially in tumors of colorectal cancer (CRC), which thus far remain uncertain. Our findings indicated that the expression of miR‐20b‐5p is negatively correlated with that of metastasis‐associated lung adenocarcinoma transcript‐1 (MALAT1, r = −0.928, p = 0.023) and Oct4 (r = −0.894, p = 0.041) in CRC cells. We hypothesized that there may be some targeted regulatory relationships among MALAT1, miR‐20b‐5p, and Oct4. We proceeded to show that both si‐MALAT1 and miR‐20b‐5p‐mimic attenuated microsphere formation and self‐renewal capacity, decreased the proportion of CSCs, and downregulated the expression of proteins associated with tumor cell stemness maintenance (Oct4, Nanog, sex‐determining region Y‐box 2, and Notch1) and cellular metabolism (glucose transporter 1, lactate dehydrogenase B, hexokinase 2, and pyruvate kinase isozyme M2) in HCT‐116 cells in vitro. In addition, a xenograft model based on Balb/c mice demonstrated that the administration of either si‐MALAT1 or miR‐20b‐5p‐mimic suppressed the tumorigenicity of HCT‐116 cells in vivo. The underlying mechanisms may involve the targeting of the tumor cell stemness maintenance‐related factor Oct4 by miR‐20b‐5p. For the first time, we present the possible underlying effects of MALAT1 in influencing the stem cell‐like properties of CRC cells. We propose that microRNAs and long noncoding RNAs have vital functions in mediating tumor stemness, which remain to be fully elucidated. We present the possible underlying effects of MALAT1 in influencing the stem cell‐like properties of colorectal cancer cells. 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This study explores the mechanisms through which CSCs maintain their stemness, especially in tumors of colorectal cancer (CRC), which thus far remain uncertain. Our findings indicated that the expression of miR‐20b‐5p is negatively correlated with that of metastasis‐associated lung adenocarcinoma transcript‐1 (MALAT1, r = −0.928, p = 0.023) and Oct4 (r = −0.894, p = 0.041) in CRC cells. We hypothesized that there may be some targeted regulatory relationships among MALAT1, miR‐20b‐5p, and Oct4. We proceeded to show that both si‐MALAT1 and miR‐20b‐5p‐mimic attenuated microsphere formation and self‐renewal capacity, decreased the proportion of CSCs, and downregulated the expression of proteins associated with tumor cell stemness maintenance (Oct4, Nanog, sex‐determining region Y‐box 2, and Notch1) and cellular metabolism (glucose transporter 1, lactate dehydrogenase B, hexokinase 2, and pyruvate kinase isozyme M2) in HCT‐116 cells in vitro. In addition, a xenograft model based on Balb/c mice demonstrated that the administration of either si‐MALAT1 or miR‐20b‐5p‐mimic suppressed the tumorigenicity of HCT‐116 cells in vivo. The underlying mechanisms may involve the targeting of the tumor cell stemness maintenance‐related factor Oct4 by miR‐20b‐5p. For the first time, we present the possible underlying effects of MALAT1 in influencing the stem cell‐like properties of CRC cells. We propose that microRNAs and long noncoding RNAs have vital functions in mediating tumor stemness, which remain to be fully elucidated. We present the possible underlying effects of MALAT1 in influencing the stem cell‐like properties of colorectal cancer cells. We propose that microRNAs and long noncoding RNAs have vital functions in mediating tumor stemness, which remain to be fully elucidated.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>31012108</pmid><doi>10.1002/jcp.28687</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-7776-7387</orcidid></addata></record>
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subjects Adenocarcinoma
Cancer
cancer stem cells
Cell self-renewal
Chemotherapy
Colorectal cancer
Colorectal carcinoma
Glucose metabolism
Glucose transporter
Hexokinase
Kinases
L-Lactate dehydrogenase
Lactate dehydrogenase
Lactic acid
Lung cancer
Lungs
MALAT1
Metastases
Metastasis
miRNA
miR‐20b‐5p/Oct4 axis
Notch1 protein
Oct-4 protein
Pyruvate kinase
Pyruvic acid
Stem cell transplantation
Stem cells
stemness
Transcription
Tumorigenicity
Tumors
Xenografts
Xenotransplantation
title Long noncoding RNA MALAT1 mediates stem cell‐like properties in human colorectal cancer cells by regulating miR‐20b‐5p/Oct4 axis
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