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Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
Published on: June 27, 2020
LncRNA NOC2L-4.1 functions as a tumor oncogene in cervical cancer progression by regulating the miR-630/YAP1 pathway
Qingwei Wang1, Jin Ding1, Guo Nan1
1Department of Gynecology and Obstetrics, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, China.
Abstract:
Long noncoding RNA (lncRNA) is a new class of noncoding RNA playing an indispensable role in different diseases by regulating miRNA. Our previous studies have suggested that miR-630 was decreased in patients with cervical cancer. Recently, studies have shown that lncRNA NOC2L-4.1 was abnormally expressed in patients with cervical cancer and can target miR-630. Therefore, we wanted to identify the integrated relationship between lncRNA NOC2L-4.1 and miR-630 in the pathological processes regarding cervical cancer either in vitro or in vivo. Quantitative reverse transcription-polymerase chain reaction detection shows that compared with human normal cervical epithelial cell, the expression of lncRNA NOC2L-4.1 was significantly increased and the expression of miR-630 was decreased in cell lines of cervical cancer. Moreover, luciferase reporter assay showed that miR-630 was a target of lncRNA NOC2L-4.1. The in vitro study found that downregulation of lncRNA NOC2L-4.1 suppressed cervical cancer cell migration (transwell assays) and proliferation (cell counting kit-8 and cloning formation assays). miR-630 specific inhibitor treatment reversed the inhibitory effect of lncRNA NOC2L-4.1 on cell proliferation and migration. Further studies also found that yes-associated protein 1 (YAP1) was the target of miR-630. Overexpression YAP1 suppressed miR-630 overexpression induced cell proliferation and inhibition of migration. Tumors induced by implantation of lncRNA NOC2L-4.1-knockdown Hela cells in nude mice showed that lncRNA NOC2L-4.1 silencing decreased the growth of tumors in both volume and weight by regulation of miR-630/YAP1. Taken together, our study reveals the important role of lncRNA NOC2L-4.1/miR-630/YAP1 regulatory network in cervical cancer, which provides new insights concerning the pathogenesis of cervical cancer.
Insights
Long noncoding RNA NOC2L-4.1 is elevated in cervical cancer and promotes tumor growth by inhibiting miR-630. Targeting this long noncoding RNA (lncRNA) and its miR-630/YAP1 pathway offers new therapeutic strategies for cervical cancer.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- Long noncoding RNAs (lncRNAs) regulate gene expression and are implicated in various diseases.
- MicroRNAs (miRNAs) are small noncoding RNAs that play crucial roles in cellular processes and disease pathogenesis.
- Previous studies indicated decreased miR-630 and abnormal lncRNA NOC2L-4.1 expression in cervical cancer.
Purpose of the Study:
- To investigate the integrated relationship between lncRNA NOC2L-4.1 and miR-630 in cervical cancer.
- To elucidate the regulatory network involving lncRNA NOC2L-4.1, miR-630, and YAP1 in cervical cancer progression.
- To assess the therapeutic potential of targeting the lncRNA NOC2L-4.1/miR-630/YAP1 axis in cervical cancer.
Main Methods:
- Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to measure gene expression.
- Luciferase reporter assay to confirm direct targeting.
- In vitro cell assays (Transwell, CCK-8, colony formation) to assess proliferation and migration.
- In vivo tumor xenograft models in nude mice.
Main Results:
- lncRNA NOC2L-4.1 expression was significantly increased, while miR-630 was decreased in cervical cancer cells.
- lncRNA NOC2L-4.1 directly targets miR-630.
- Downregulation of lncRNA NOC2L-4.1 inhibited cervical cancer cell migration and proliferation, an effect reversed by miR-630 inhibition.
- Yes-associated protein 1 (YAP1) was identified as a target of miR-630.
- lncRNA NOC2L-4.1 silencing reduced tumor growth in vivo via the miR-630/YAP1 pathway.
Conclusions:
- lncRNA NOC2L-4.1 promotes cervical cancer progression by sponging miR-630 and upregulating YAP1.
- The lncRNA NOC2L-4.1/miR-630/YAP1 regulatory network is crucial in cervical cancer pathogenesis.
- Targeting this network presents a potential therapeutic strategy for cervical cancer.
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