miR-4293 upregulates lncRNA WFDC21P by suppressing mRNA-decapping enzyme 2 to promote lung carcinoma proliferation

• Published in: Cell death & disease 2021-07, Vol.12 (8), p.735-13, Article 735
• Main Authors: Zhang, Qian, Yan, Yun-Fei, Lv, Qing, Li, You-Jie, Wang, Ran-Ran, Sun, Guang-Bin, Pan, Li, Hu, Jin-Xia, Xie, Ning, Zhang, Can, Tian, Bao-Cheng, Jiao, Fei, Xu, Sen, Wang, Ping-Yu, Xie, Shu-Yang
• Format: Article
• Language: English
• Subjects: 13/31; 38/1; 38/109; 38/89; 42/44; 45/90; 45/91; 631/337/384/2568; 692/699/67/395; 96/2; 96/31; Adult; Aged; Animals; Antibodies; Apoptosis; Apoptosis - genetics; Base Sequence; Biochemistry; Biomedical and Life Sciences; Cancer; Carcinogenesis - genetics; Carcinogenesis - pathology; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Cell Biology; Cell Culture; Cell Line, Tumor; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Enzymes; Female; Gene expression; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Gene regulation; Humans; Immunology; Life Sciences; Lung cancer; Lung carcinoma; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Metastases; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miRNA; Models, Biological; Non-coding RNA; Non-small cell lung carcinoma; Post-transcription; Protein Binding; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Small cell lung carcinoma; STAT3 Transcription Factor - metabolism; Therapeutic targets; Up-Regulation - genetics; Xenografts
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-021-04021-y

Non-coding RNAs (ncRNAs) involve in diverse biological processes by post-transcriptional regulation of gene expression. Emerging evidence shows that miRNA-4293 plays a significant role in the development of non-small cell lung cancer. However, the oncogenic functions of miR-4293 have not been studied. Our results demonstrated that miR-4293 expression is markedly enhanced in lung carcinoma tissue and cells. Moreover, miR-4293 promotes tumor cell proliferation and metastasis but suppresses apoptosis. Mechanistic investigations identified mRNA-decapping enzyme 2 (DCP2) as a target of miR-4293 and its expression is suppressed by miR-4293. DCP2 can directly or indirectly bind to WFDC21P and downregulates its expression. Consequently, miR-4293 can further promote WFDC21P expression by regulating DCP2. With a positive correlation to miR-4293 expression, WFDC21P also plays an oncogenic role in lung carcinoma. Furthermore, knockdown of WFDC21P results in functional attenuation of miR-4293 on tumor promotion. In vivo xenograft growth is also promoted by both miR-4293 and WFDC21P. Overall, our results establish oncogenic roles for both miR-4293 and WFDC21P and demonstrate that interactions between miRNAs and lncRNAs through DCP2 are important in the regulation of carcinoma pathogenesis. These results provided a valuable theoretical basis for the discovery of lung carcinoma therapeutic targets and diagnostic markers based on miR-4293 and WFDC21P.