Involvement of Dual Strands of <i>miR-143</i> (<i>miR-143-5p</i> and <i>miR-143-3p</i>) and Their Target Oncogenes in the Molecular Pathogenesis of Lung Adenocarcinoma
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 bo...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-09-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/20/18/4482 |
| _version_ | 1811211011723624448 |
|---|---|
| author | Hiroki Sanada Naohiko Seki Keiko Mizuno Shunsuke Misono Akifumi Uchida Yasutaka Yamada Shogo Moriya Naoko Kikkawa Kentaro Machida Tomohiro Kumamoto Takayuki Suetsugu Hiromasa Inoue |
| author_facet | Hiroki Sanada Naohiko Seki Keiko Mizuno Shunsuke Misono Akifumi Uchida Yasutaka Yamada Shogo Moriya Naoko Kikkawa Kentaro Machida Tomohiro Kumamoto Takayuki Suetsugu Hiromasa Inoue |
| author_sort | Hiroki Sanada |
| collection | DOAJ |
| description | 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 <i>miR-143</i> 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 <i>miR-143-5p</i> molecular networks in LUAD using genome-wide gene expression and miRNA database analyses. Twenty-two genes were identified as potential <i>miR-143-5p</i>-controlled genes in LUAD cells. Interestingly, the expression of 11 genes (<i>MCM4</i>, <i>RAD51</i>, <i>FAM111B</i>, <i>CLGN</i>, <i>KRT80</i>, <i>GPC1</i>, <i>MTL5</i>, <i>NETO2</i>, <i>FANCA</i>, <i>MTFR1</i>, and <i>TTLL12</i>) was a prognostic factor for the patients with LUAD. Furthermore, knockdown assays using siRNAs showed that downregulation of <i>MCM4</i> suppressed cell growth, migration, and invasion in LUAD cells. Aberrant expression of <i>MCM4</i> was confirmed in the clinical specimens of LUAD. Thus, we showed that <i>miR-143-5p</i> 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. |
| first_indexed | 2024-04-12T05:05:47Z |
| format | Article |
| id | doaj.art-28d8459956ce42bb8111ab17be891b39 |
| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-12T05:05:47Z |
| publishDate | 2019-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-28d8459956ce42bb8111ab17be891b392022-12-22T03:46:53ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-09-012018448210.3390/ijms20184482ijms20184482Involvement of Dual Strands of <i>miR-143</i> (<i>miR-143-5p</i> and <i>miR-143-3p</i>) and Their Target Oncogenes in the Molecular Pathogenesis of Lung AdenocarcinomaHiroki Sanada0Naohiko Seki1Keiko Mizuno2Shunsuke Misono3Akifumi Uchida4Yasutaka Yamada5Shogo Moriya6Naoko Kikkawa7Kentaro Machida8Tomohiro Kumamoto9Takayuki Suetsugu10Hiromasa Inoue11Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, JapanDepartment of Functional Genomics, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, JapanDepartment of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, JapanDepartment of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, JapanDepartment of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, JapanDepartment of Functional Genomics, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, JapanDepartment of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, JapanDepartment of Functional Genomics, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, JapanDepartment of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, JapanDepartment of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, JapanDepartment of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, JapanDepartment of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, JapanOur 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 <i>miR-143</i> 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 <i>miR-143-5p</i> molecular networks in LUAD using genome-wide gene expression and miRNA database analyses. Twenty-two genes were identified as potential <i>miR-143-5p</i>-controlled genes in LUAD cells. Interestingly, the expression of 11 genes (<i>MCM4</i>, <i>RAD51</i>, <i>FAM111B</i>, <i>CLGN</i>, <i>KRT80</i>, <i>GPC1</i>, <i>MTL5</i>, <i>NETO2</i>, <i>FANCA</i>, <i>MTFR1</i>, and <i>TTLL12</i>) was a prognostic factor for the patients with LUAD. Furthermore, knockdown assays using siRNAs showed that downregulation of <i>MCM4</i> suppressed cell growth, migration, and invasion in LUAD cells. Aberrant expression of <i>MCM4</i> was confirmed in the clinical specimens of LUAD. Thus, we showed that <i>miR-143-5p</i> 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.https://www.mdpi.com/1422-0067/20/18/4482lung adenocarcinomamicroRNA<i>miR-143-5p</i><i>miR-143-3p</i>tumor-suppressor<i>MCM4</i> |
| spellingShingle | Hiroki Sanada Naohiko Seki Keiko Mizuno Shunsuke Misono Akifumi Uchida Yasutaka Yamada Shogo Moriya Naoko Kikkawa Kentaro Machida Tomohiro Kumamoto Takayuki Suetsugu Hiromasa Inoue Involvement of Dual Strands of <i>miR-143</i> (<i>miR-143-5p</i> and <i>miR-143-3p</i>) and Their Target Oncogenes in the Molecular Pathogenesis of Lung Adenocarcinoma International Journal of Molecular Sciences lung adenocarcinoma microRNA <i>miR-143-5p</i> <i>miR-143-3p</i> tumor-suppressor <i>MCM4</i> |
| title | Involvement of Dual Strands of <i>miR-143</i> (<i>miR-143-5p</i> and <i>miR-143-3p</i>) and Their Target Oncogenes in the Molecular Pathogenesis of Lung Adenocarcinoma |
| title_full | Involvement of Dual Strands of <i>miR-143</i> (<i>miR-143-5p</i> and <i>miR-143-3p</i>) and Their Target Oncogenes in the Molecular Pathogenesis of Lung Adenocarcinoma |
| title_fullStr | Involvement of Dual Strands of <i>miR-143</i> (<i>miR-143-5p</i> and <i>miR-143-3p</i>) and Their Target Oncogenes in the Molecular Pathogenesis of Lung Adenocarcinoma |
| title_full_unstemmed | Involvement of Dual Strands of <i>miR-143</i> (<i>miR-143-5p</i> and <i>miR-143-3p</i>) and Their Target Oncogenes in the Molecular Pathogenesis of Lung Adenocarcinoma |
| title_short | Involvement of Dual Strands of <i>miR-143</i> (<i>miR-143-5p</i> and <i>miR-143-3p</i>) and Their Target Oncogenes in the Molecular Pathogenesis of Lung Adenocarcinoma |
| title_sort | involvement of dual strands of i mir 143 i i mir 143 5p i and i mir 143 3p i and their target oncogenes in the molecular pathogenesis of lung adenocarcinoma |
| topic | lung adenocarcinoma microRNA <i>miR-143-5p</i> <i>miR-143-3p</i> tumor-suppressor <i>MCM4</i> |
| url | https://www.mdpi.com/1422-0067/20/18/4482 |
| work_keys_str_mv | AT hirokisanada involvementofdualstrandsofimir143iimir1435piandimir1433piandtheirtargetoncogenesinthemolecularpathogenesisoflungadenocarcinoma AT naohikoseki involvementofdualstrandsofimir143iimir1435piandimir1433piandtheirtargetoncogenesinthemolecularpathogenesisoflungadenocarcinoma AT keikomizuno involvementofdualstrandsofimir143iimir1435piandimir1433piandtheirtargetoncogenesinthemolecularpathogenesisoflungadenocarcinoma AT shunsukemisono involvementofdualstrandsofimir143iimir1435piandimir1433piandtheirtargetoncogenesinthemolecularpathogenesisoflungadenocarcinoma AT akifumiuchida involvementofdualstrandsofimir143iimir1435piandimir1433piandtheirtargetoncogenesinthemolecularpathogenesisoflungadenocarcinoma AT yasutakayamada involvementofdualstrandsofimir143iimir1435piandimir1433piandtheirtargetoncogenesinthemolecularpathogenesisoflungadenocarcinoma AT shogomoriya involvementofdualstrandsofimir143iimir1435piandimir1433piandtheirtargetoncogenesinthemolecularpathogenesisoflungadenocarcinoma AT naokokikkawa involvementofdualstrandsofimir143iimir1435piandimir1433piandtheirtargetoncogenesinthemolecularpathogenesisoflungadenocarcinoma AT kentaromachida involvementofdualstrandsofimir143iimir1435piandimir1433piandtheirtargetoncogenesinthemolecularpathogenesisoflungadenocarcinoma AT tomohirokumamoto involvementofdualstrandsofimir143iimir1435piandimir1433piandtheirtargetoncogenesinthemolecularpathogenesisoflungadenocarcinoma AT takayukisuetsugu involvementofdualstrandsofimir143iimir1435piandimir1433piandtheirtargetoncogenesinthemolecularpathogenesisoflungadenocarcinoma AT hiromasainoue involvementofdualstrandsofimir143iimir1435piandimir1433piandtheirtargetoncogenesinthemolecularpathogenesisoflungadenocarcinoma |