Circular RNA 101368/miR-200a axis modulates the migration of hepatocellular carcinoma through HMGB1/RAGE signaling

Shaling Li, Huimin Gu, Yan Huang, Qian Peng, Rongrong Zhou, Panpan Yi, Ruochan Chen, Zebing Huang, Xingwang Hu, Yun Huang, Daolin Tang

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Hepatocellular carcinoma (HCC), one of the most common type of cancers, is highly refractory to most systemic therapies. Understanding the genomic dysregulations, in particularly non-coding RNA (ncRNA) dysregulations, in HCC may provide novel strategies to HCC treatment. In our previous study, we demonstrated the key role of miR-200a-mediated HMGB1/RAGE signaling in HCC carcinogenesis. In the present study, we identified circular RNA (circRNA)-miRNA pair that might modulate the migration of HCC cell lines based on previously reported GEO database (GSE78520 and GSE43445) and investigated the function and molecular mechanism. circRNA-101368 was predicted by lncTar to target miR-200a, and the expression of circRNA-101368 was significantly upregulated in HCC tissue samples; the overexpression of circRNA-101368 was correlated with poorer prognosis in patients with HCC. Moreover, circRNA-101368 knockdown suppressed the migration and the protein levels of HMGB1, RAGE and NF-κB, while increased the E-Cadherin expression in HCC cell lines. As confirmed by luciferase reporter and RNA immunoprecipitation assays, circRNA-101368 directly bound to miR-200a to negatively regulate each other. The effect of circRNA-101368 knockdown on cell migration and HMGB1/RAGE signaling could be partially attenuated by miR-200a inhibition. In tissue samples, miR-200a was negatively correlated with circRNA-101368 and HMGB1, respectively, whereas circRNA-101368 and HMGB1 was positively correlated. Taken together, we demonstrated a network of circRNAs-miRNA-mRNA in HCC and provided a novel mechanism of HCC cell migration regulation.

Original languageEnglish (US)
Pages (from-to)2349-2359
Number of pages11
JournalCell Cycle
Volume17
Issue number19-20
DOIs
StatePublished - Oct 18 2018
Externally publishedYes

Fingerprint

HMGB1 Protein
Hepatocellular Carcinoma
MicroRNAs
Cell Movement
circular RNA
Cell Line
Untranslated RNA
Cadherins
Luciferases
Immunoprecipitation
Carcinogenesis
Databases
RNA

Keywords

  • circRNA-101368
  • Hepatocellular carcinoma (HCC)
  • HMGB1

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

Circular RNA 101368/miR-200a axis modulates the migration of hepatocellular carcinoma through HMGB1/RAGE signaling. / Li, Shaling; Gu, Huimin; Huang, Yan; Peng, Qian; Zhou, Rongrong; Yi, Panpan; Chen, Ruochan; Huang, Zebing; Hu, Xingwang; Huang, Yun; Tang, Daolin.

In: Cell Cycle, Vol. 17, No. 19-20, 18.10.2018, p. 2349-2359.

Research output: Contribution to journalArticle

Li, S, Gu, H, Huang, Y, Peng, Q, Zhou, R, Yi, P, Chen, R, Huang, Z, Hu, X, Huang, Y & Tang, D 2018, 'Circular RNA 101368/miR-200a axis modulates the migration of hepatocellular carcinoma through HMGB1/RAGE signaling', Cell Cycle, vol. 17, no. 19-20, pp. 2349-2359. https://doi.org/10.1080/15384101.2018.1526599
Li, Shaling ; Gu, Huimin ; Huang, Yan ; Peng, Qian ; Zhou, Rongrong ; Yi, Panpan ; Chen, Ruochan ; Huang, Zebing ; Hu, Xingwang ; Huang, Yun ; Tang, Daolin. / Circular RNA 101368/miR-200a axis modulates the migration of hepatocellular carcinoma through HMGB1/RAGE signaling. In: Cell Cycle. 2018 ; Vol. 17, No. 19-20. pp. 2349-2359.
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AU - Li, Shaling

AU - Gu, Huimin

AU - Huang, Yan

AU - Peng, Qian

AU - Zhou, Rongrong

AU - Yi, Panpan

AU - Chen, Ruochan

AU - Huang, Zebing

AU - Hu, Xingwang

AU - Huang, Yun

AU - Tang, Daolin

PY - 2018/10/18

Y1 - 2018/10/18

N2 - Hepatocellular carcinoma (HCC), one of the most common type of cancers, is highly refractory to most systemic therapies. Understanding the genomic dysregulations, in particularly non-coding RNA (ncRNA) dysregulations, in HCC may provide novel strategies to HCC treatment. In our previous study, we demonstrated the key role of miR-200a-mediated HMGB1/RAGE signaling in HCC carcinogenesis. In the present study, we identified circular RNA (circRNA)-miRNA pair that might modulate the migration of HCC cell lines based on previously reported GEO database (GSE78520 and GSE43445) and investigated the function and molecular mechanism. circRNA-101368 was predicted by lncTar to target miR-200a, and the expression of circRNA-101368 was significantly upregulated in HCC tissue samples; the overexpression of circRNA-101368 was correlated with poorer prognosis in patients with HCC. Moreover, circRNA-101368 knockdown suppressed the migration and the protein levels of HMGB1, RAGE and NF-κB, while increased the E-Cadherin expression in HCC cell lines. As confirmed by luciferase reporter and RNA immunoprecipitation assays, circRNA-101368 directly bound to miR-200a to negatively regulate each other. The effect of circRNA-101368 knockdown on cell migration and HMGB1/RAGE signaling could be partially attenuated by miR-200a inhibition. In tissue samples, miR-200a was negatively correlated with circRNA-101368 and HMGB1, respectively, whereas circRNA-101368 and HMGB1 was positively correlated. Taken together, we demonstrated a network of circRNAs-miRNA-mRNA in HCC and provided a novel mechanism of HCC cell migration regulation.

AB - Hepatocellular carcinoma (HCC), one of the most common type of cancers, is highly refractory to most systemic therapies. Understanding the genomic dysregulations, in particularly non-coding RNA (ncRNA) dysregulations, in HCC may provide novel strategies to HCC treatment. In our previous study, we demonstrated the key role of miR-200a-mediated HMGB1/RAGE signaling in HCC carcinogenesis. In the present study, we identified circular RNA (circRNA)-miRNA pair that might modulate the migration of HCC cell lines based on previously reported GEO database (GSE78520 and GSE43445) and investigated the function and molecular mechanism. circRNA-101368 was predicted by lncTar to target miR-200a, and the expression of circRNA-101368 was significantly upregulated in HCC tissue samples; the overexpression of circRNA-101368 was correlated with poorer prognosis in patients with HCC. Moreover, circRNA-101368 knockdown suppressed the migration and the protein levels of HMGB1, RAGE and NF-κB, while increased the E-Cadherin expression in HCC cell lines. As confirmed by luciferase reporter and RNA immunoprecipitation assays, circRNA-101368 directly bound to miR-200a to negatively regulate each other. The effect of circRNA-101368 knockdown on cell migration and HMGB1/RAGE signaling could be partially attenuated by miR-200a inhibition. In tissue samples, miR-200a was negatively correlated with circRNA-101368 and HMGB1, respectively, whereas circRNA-101368 and HMGB1 was positively correlated. Taken together, we demonstrated a network of circRNAs-miRNA-mRNA in HCC and provided a novel mechanism of HCC cell migration regulation.

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KW - Hepatocellular carcinoma (HCC)

KW - HMGB1

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