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Molecular mechanism of miR-34b-5p and RNA binding protein HuR binding to lncRNA OIP5-AS1 in colon cancer cells

Cancer Gene Therapy volume 29, pages 612–624 (2022)Cite this article

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Abstract

Colon cancer (CC) is a leading cause of cancer-related death. Long non-coding RNA OIP5-AS1 (lncRNA OIP5-AS1) expression pattern has been studied in many cancers. We aimed to identify the mechanism of lncRNA OIP5-AS1 in CC development. OIP5-AS1 expression pattern in CC tissues and cells was detected and the relation between OIP5-AS1 level and CC prognosis was analyzed. The proliferation, migration and invasion of CC cells were detected after silencing or overexpression of OIP5-AS1. Tumor xenograft in nude mice was established to verify the effect of OIP5-AS1 in vivo. The interaction between HuR protein and OIP5-AS1 and the interaction of miR-34b-5p with HuR and OIP5-AS1 were measured. OIP5-AS1 was highly expressed in CC and associated with poor prognosis. Silencing OIP5-AS1 inhibited CC cell malignant behaviors and inhibited the growth rate and tumor weight. In the mechanism, HuR bound to OIP5-AS1 and stabilized OIP5-AS1 expression. Both miR-34-5p and HuR bind to OIP5 and oppositely affect its expression. miR-34b-5p inhibited the proliferation and invasion of CC cells by inhibiting OIP5-AS1 and PI3K/Akt pathway. miR-34b-5p inhibited CC growth by inhibiting OIP5-AS1. Collectively, miR-34b-5p targets HuR and miR-34b-5p binds to OIP5-AS1 with HuR, thus inhibiting OIP5-AS1 and PI3K/Akt pathway and CC progression.

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Fig. 1: OIP5-AS1 is highly expressed in CC cells.
Fig. 2: Silencing OIP5-AS1 can inhibit the proliferation, migration and invasion of CC cells.
Fig. 3: Silencing OIP5-AS1 inhibits the growth of CC cells in vivo.
Fig. 4: HuR binds to OIP5-AS1 in CC cells.
Fig. 5: miR-34b-5p targets ELAVL1 (HuR).
Fig. 6: miR-34b-5p and HuR bind to OIP5-AS1, thus reducing OIP5-AS1 expression.
Fig. 7: miR-34b-5p inhibits the proliferation and invasion of CC cells by inhibiting OIP5-AS1 and the PI3K/Akt pathway.
Fig. 8: miR-34b-5p inhibits the proliferation and invasion of CC cells in vivo by inhibiting OIP5-AS1.
Fig. 9: miR-34b-5p specifically inhibits the expression of ELAVL1 (HuR).

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Data availability

The data that support this study are available from the corresponding author upon reasonable request.

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Authors and Affiliations

  1. Departmeng of Gastroenterology, Shengjing hospital of China Medical University, Shenyang, 110004, Liaoning Province, China

    Yan Wang

  2. College of Basic Medical Science, China Medical University, Shenyang, 110122, Liaoning Province, China

    Changkun Lin & Yang Liu

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Y.W.: Conceptualization. C.L.: Writing—original draft preparation. Y.L.: Writing—reviewing and editing.

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Correspondence to Yan Wang.

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This study was performed with the approval of the Clinical Ethical Committee of Shengjing Hospital. Informed consent was received from all subjects. The animal experiments were conducted based on minimized animal number and the least pains.

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Wang, Y., Lin, C. & Liu, Y. Molecular mechanism of miR-34b-5p and RNA binding protein HuR binding to lncRNA OIP5-AS1 in colon cancer cells. Cancer Gene Ther 29, 612–624 (2022). https://doi.org/10.1038/s41417-021-00342-4

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