Molecular Pathogenesis of Colorectal Cancer: Impact of Oncogenic Targets Regulated by Tumor Suppressive miR-139-3p

Yasudome, Ryutaro; Seki, Naohiko; Asai, Shunichi; Goto, Yusuke; Kita, Yoshiaki; Hozaka, Yuto; Wada, Mitsuru; Tanabe, Kan; Idichi, Tetsuya; Mori, Shinichiro; Ohtsuka, Takao

doi:10.3390/ijms231911616

Cited by 10 publications

(10 citation statements)

References 57 publications

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“…A unique feature of miRNAs is that the target genes of a specific miRNA differ depending on the cell. Our previous studies confirmed that the same tumor-suppressive miRNA regulates different genes depending on the cancer type [11][12][13][14]. The aim of this study was to confirm the tumor-suppressive function of miR-139-3p and to clarify the molecular networks controlled by miR-139-3p in LUAD cells.…”

Section: Introductionmentioning

confidence: 58%

“…We have generated miRNA expression signatures for various cancer types using RNA sequencing and selected tumor-suppressive miRNA candidates based on those signatures [10,[35][36][37]. Of these candidates, we identified downregulation and tumor-suppressive functions of miR-139-3p in various cancers, including bladder cancer, renal cell carcinoma, head and neck squamous cell carcinoma, and colorectal cancer [11][12][13][14]. Here, we showed that miR-139-3p functions as a tumor-suppressive miRNA in LUAD in addition to other cancer types.…”

Section: Discussionmentioning

confidence: 99%

“…Analysis of this signature showed that both the guide and passenger strands of pre-miR-139 (miR-139-5p and miR-139-3p, respectively) were downregulated in LUAD tissues. Focusing on miR-139-3p, we have identified its tumor-suppressive roles and cancer-promoting target genes in various cancer types (e.g., bladder cancer, renal cell carcinoma, oral cancer, and colorectal cancer) [11][12][13][14]. A unique feature of miRNAs is that the target genes of a specific miRNA differ depending on the cell.…”

Section: Introductionmentioning

confidence: 99%

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Identification of Tumor-Suppressive miR-139-3p-Regulated Genes: TRIP13 as a Therapeutic Target in Lung Adenocarcinoma

Hagihara,

Tomioka,

Suetsugu

et al. 2023

Cancers

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Analyses of our microRNA (miRNA) expression signature combined with The Cancer Genome Atlas (TCGA) data revealed that both strands of pre-miR-139 (miR-139-5p, the guide strand, and miR-139-3p, the passenger strand) are significantly downregulated in lung adenocarcinoma (LUAD) clinical specimens. Functional analyses of LUAD cells ectopically expressing miR-139-3p showed significant suppression of their aggressiveness (e.g., cancer cell proliferation, migration, and invasion). The involvement of the passenger strand, miR-139-3p, in LUAD pathogenesis, is an interesting finding contributing to the elucidation of unknown molecular networks in LUAD. Of 1108 genes identified as miR-139-3p targets in LUAD cells, 21 were significantly upregulated in LUAD tissues according to TCGA analysis, and their high expression negatively affected the prognosis of LUAD patients. We focused on thyroid hormone receptor interactor 13 (TRIP13) and investigated its cancer-promoting functions in LUAD cells. Luciferase assays showed that miR-139-3p directly regulated TRIP13. siRNA-mediated TRIP13 knockdown and TRIP13 inhibition by a specific inhibitor (DCZ0415) attenuated the malignant transformation of LUAD cells. Interestingly, when used in combination with anticancer drugs (cisplatin and carboplatin), DCZ0415 exerted synergistic effects on cell proliferation suppression. Identifying the molecular pathways regulated by tumor-suppressive miRNAs (including passenger strands) may aid in the discovery of diagnostic markers and therapeutic targets for LUAD.

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Section: Introductionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Identification of Tumor-Suppressive miR-139-3p-Regulated Genes: TRIP13 as a Therapeutic Target in Lung Adenocarcinoma

Hagihara,

Tomioka,

Suetsugu

et al. 2023

Cancers

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“…Vector construction and dual-luciferase reporter assays were performed as described in our previous studies [ 19 , 31 ]. The vector insertion sequences are shown in Figure S1 , and the reagents used are listed in Table S2 .…”

Section: Methodsmentioning

confidence: 99%

Oncogenic Targets Regulated by Tumor-Suppressive miR-30c-1-3p and miR-30c-2-3p: TRIP13 Facilitates Cancer Cell Aggressiveness in Breast Cancer

Mitsueda,

Toda,

Shinden

et al. 2023

Cancers

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Accumulating evidence suggests that the miR-30 family act as critical players (tumor-suppressor or oncogenic) in a wide range of human cancers. Analysis of microRNA (miRNA) expression signatures and The Cancer Genome Atlas (TCGA) database revealed that that two passenger strand miRNAs, miR-30c-1-3p and miR-30c-2-3p, were downregulated in cancer tissues, and their low expression was closely associated with worse prognosis in patients with BrCa. Functional assays showed that miR-30c-1-3p and miR-30c-2-3p overexpression significantly inhibited cancer cell aggressiveness, suggesting these two miRNAs acted as tumor-suppressors in BrCa cells. Notably, involvement of passenger strands of miRNAs is a new concept of cancer research. Further analyses showed that seven genes (TRIP13, CCNB1, RAD51, PSPH, CENPN, KPNA2, and MXRA5) were putative targets of miR-30c-1-3p and miR-30c-2-3p in BrCa cells. Expression of seven genes were upregulated in BrCa tissues and predicted a worse prognosis of the patients. Among these genes, we focused on TRIP13 and investigated the functional significance of this gene in BrCa cells. Luciferase reporter assays showed that TRIP13 was directly regulated by these two miRNAs. TRIP13 knockdown using siRNA attenuated BrCa cell aggressiveness. Inactivation of TRIP13 using a specific inhibitor prevented the malignant transformation of BrCa cells. Exploring the molecular networks controlled by miRNAs, including passenger strands, will facilitate the identification of diagnostic markers and therapeutic target molecules in BrCa.

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“…Klimaszewska-Wisniewska et al proved that SPDL1 upregulation in CRC cells indicates chromosomal instability and long survival [ 8 ]. Yasudome et al introduced a new concept referring to the possible interaction between microRNA139 (miR-139-3p) and keratin 80, which plays a potential tumor-suppressive role [ 9 ]. Pietras et al proved that CRC cell proliferation and vascular migration are mediated by major vault proteins, which possess barrel-like structures [ 10 ].…”

mentioning

confidence: 99%

Molecular Diagnostics, Pathology and Biomarkers of Gastrointestinal Neoplasms

Gurzu

2023

IJMS

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Molecular Pathogenesis of Colorectal Cancer: Impact of Oncogenic Targets Regulated by Tumor Suppressive miR-139-3p

Cited by 10 publications

References 57 publications

Identification of Tumor-Suppressive miR-139-3p-Regulated Genes: TRIP13 as a Therapeutic Target in Lung Adenocarcinoma

Identification of Tumor-Suppressive miR-139-3p-Regulated Genes: TRIP13 as a Therapeutic Target in Lung Adenocarcinoma

Oncogenic Targets Regulated by Tumor-Suppressive miR-30c-1-3p and miR-30c-2-3p: TRIP13 Facilitates Cancer Cell Aggressiveness in Breast Cancer

Molecular Diagnostics, Pathology and Biomarkers of Gastrointestinal Neoplasms

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