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Dual-strand tumor suppressor miR-193b-3p and -5p inhibit malignant phenotypes of lung cancer by suppressing their common targets

Choi, Kyung Hee, Shin, Chang Hoon, Lee, Woo Joo, Ji, Haein, Kim, Hyeon Ho·2019·Bioscience Reports
DOI 10.1042/bsr20190634PMC PMC6630026
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Abstract

Emerging studies suggest that microRNAs (miRNAs) play multiple roles in cancer malignancy, including proliferation and acquisition of metastatic potential. Differentially expressed miRNAs responsible for the malignancy of lung cancer were searched by miRNA microarray using a previously established brain metastatic lung cancer model. Twenty-five miRNAs were down-regulated in brain metastatic lung cancer cells. Among those, miR-193b-3p and -5p were chosen for further studies. Their function in metastatic potential and proliferation was examined using Transwell invasion, wound healing, and colony forming assays. The underlying mechanism of tumor-suppressor miR-193b-3p and -5p was explored using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), Western blot, Argonaute 2-RNA immunoprecipitation (Ago2-RIP), and reporter assays. Both strands of miR-193b were down-regulated in brain metastatic lung cancer cells and in tissues from lung cancer patients. Overexpression of miR-193b-3p and -5p inhibited invasive and migratory activities and diminished clonogenic ability. Conversely, inhibition of miR-193b-3p or -5p increased the metastatic potential and colony forming ability. Cyclin D1 (CCND1), Ajuba LIM Protein (AJUBA), and heart development protein with EGF like domains 1 (HEG1) were identified as common target genes of miR-193b-3p and -5p. A reporter assay and an Ago2-RIP experiment showed that both miRNAs directly bind to the 3′ untranslated region (3′UTR) of the target mRNA. Knockdown of target gene reduced the proliferative and metastatic potential of primary and metastatic lung cancer cells. Our results demonstrate miR-193b is a dual-strand tumor suppressor and a novel therapeutic target for lung cancer.

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  • Both miR-193b strands appear to target Cyclin-D (CCND1), Ajuba LIM protein (AJUBA) and heart developmental protein with EGF like domains (HEG1), and knocking down those targets phenocopies restored miR-193b levels.

    “Both strands appear to target Cyclin‐D (CCND1), Ajuba LIM protein (AJUBA) and heart developmental protein with EGF like domains (HEG1) and knocking down those targets phenocopies restored miR‐193b levels (Choi et al., 2019).”

    From microRNA strand selection: Unwinding the rules (2021) · cites this paper as Choi et al., 2019

  • Both miR-193b (3p) and miR-193b* (5p) are down regulated in lung cancer and restoring the levels of either strand suppresses malignant phenotypes including metastatic potential and cell proliferation.

    “In another example, both miR‐193b (3p) and miR‐193b* (5p) are down regulated in lung cancer and restoring the levels of either strand suppresses malignant phenotypes including metastatic potential and cell proliferation (Choi et al., 2019), (Table 1).”

    From microRNA strand selection: Unwinding the rules (2021) · cites this paper as Choi et al., 2019

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Research works printed but not linked: 46

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Cited by

Sorted by citations

Authors
Choi, K. H., Shin, C. H., Lee, W. J., Ji, H., & Kim, H. H.
Affiliations
Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea
ORCID
Kim, Hyeon Ho
Venue
Bioscience Reports
Publisher
Portland Press Ltd.
Published
2019-07
Volume
39
Issue
7
ISSN
  • 0144-8463
  • 1573-4935
DOI
10.1042/bsr20190634
PMC
PMC6630026
Cited by
36
References
0
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor, 80 d)

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