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10.3390/ijms20184482
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Article

Involvement of Dual Strands of miR-143 (miR-143-5p and miR-143-3p) and Their Target Oncogenes in the Molecular Pathogenesis of Lung Adenocarcinoma

by
Hiroki Sanada
1,
Naohiko Seki
2,*,
Keiko Mizuno
1,
Shunsuke Misono
1,
Akifumi Uchida
1,
Yasutaka Yamada
2,
Shogo Moriya
3,
Naoko Kikkawa
2,
Kentaro Machida
1,
Tomohiro Kumamoto
1,
Takayuki Suetsugu
1 and
Hiromasa Inoue
1,*
1
Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan
2
Department of Functional Genomics, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan
3
Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(18), 4482; https://doi.org/10.3390/ijms20184482
Submission received: 30 July 2019 / Revised: 2 September 2019 / Accepted: 9 September 2019 / Published: 11 September 2019
(This article belongs to the Special Issue The Role of Non-Coding RNAs in Human Lung Health and Disease)
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Abstract

Our analyses of tumor-suppressive microRNAs (miRNAs) and their target oncogenes have identified novel molecular networks in lung adenocarcinoma (LUAD). Moreover, our recent studies revealed that some passenger strands of miRNAs contribute to cancer cell malignant transformation. Downregulation of both strands of the miR-143 duplex was observed in LUAD clinical specimens. Ectopic expression of these miRNAs suppressed malignant phenotypes in cancer cells, suggesting that these miRNAs have tumor-suppressive activities in LUAD cells. Here, we evaluated miR-143-5p molecular networks in LUAD using genome-wide gene expression and miRNA database analyses. Twenty-two genes were identified as potential miR-143-5p-controlled genes in LUAD cells. Interestingly, the expression of 11 genes (MCM4, RAD51, FAM111B, CLGN, KRT80, GPC1, MTL5, NETO2, FANCA, MTFR1, and TTLL12) was a prognostic factor for the patients with LUAD. Furthermore, knockdown assays using siRNAs showed that downregulation of MCM4 suppressed cell growth, migration, and invasion in LUAD cells. Aberrant expression of MCM4 was confirmed in the clinical specimens of LUAD. Thus, we showed that miR-143-5p and its target genes were involved in the molecular pathogenesis of LUAD. Identification of tumor-suppressive miRNAs and their target oncogenes may be an effective strategy for elucidation of the molecular oncogenic networks of this disease.
Keywords: lung adenocarcinoma; microRNA; miR-143-5p; miR-143-3p; tumor-suppressor; MCM4 lung adenocarcinoma; microRNA; miR-143-5p; miR-143-3p; tumor-suppressor; MCM4

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MDPI and ACS Style

Sanada, H.; Seki, N.; Mizuno, K.; Misono, S.; Uchida, A.; Yamada, Y.; Moriya, S.; Kikkawa, N.; Machida, K.; Kumamoto, T.; et al. Involvement of Dual Strands of miR-143 (miR-143-5p and miR-143-3p) and Their Target Oncogenes in the Molecular Pathogenesis of Lung Adenocarcinoma. Int. J. Mol. Sci. 2019, 20, 4482. https://doi.org/10.3390/ijms20184482

AMA Style

Sanada H, Seki N, Mizuno K, Misono S, Uchida A, Yamada Y, Moriya S, Kikkawa N, Machida K, Kumamoto T, et al. Involvement of Dual Strands of miR-143 (miR-143-5p and miR-143-3p) and Their Target Oncogenes in the Molecular Pathogenesis of Lung Adenocarcinoma. International Journal of Molecular Sciences. 2019; 20(18):4482. https://doi.org/10.3390/ijms20184482

Chicago/Turabian Style

Sanada, Hiroki, Naohiko Seki, Keiko Mizuno, Shunsuke Misono, Akifumi Uchida, Yasutaka Yamada, Shogo Moriya, Naoko Kikkawa, Kentaro Machida, Tomohiro Kumamoto, and et al. 2019. "Involvement of Dual Strands of miR-143 (miR-143-5p and miR-143-3p) and Their Target Oncogenes in the Molecular Pathogenesis of Lung Adenocarcinoma" International Journal of Molecular Sciences 20, no. 18: 4482. https://doi.org/10.3390/ijms20184482

APA Style

Sanada, H., Seki, N., Mizuno, K., Misono, S., Uchida, A., Yamada, Y., Moriya, S., Kikkawa, N., Machida, K., Kumamoto, T., Suetsugu, T., & Inoue, H. (2019). Involvement of Dual Strands of miR-143 (miR-143-5p and miR-143-3p) and Their Target Oncogenes in the Molecular Pathogenesis of Lung Adenocarcinoma. International Journal of Molecular Sciences, 20(18), 4482. https://doi.org/10.3390/ijms20184482

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