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Long Non-Coding RNA TP73-AS1 Promotes the Development of Lung Cancer by Targeting the miR-27b-3p/LAPTM4B Axis
Qingfeng Jiang1, Wenqun Xing1, Jinhua Cheng1
1Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, People's Republic of China.
Purpose:
Long non-coding RNA P73 antisense RNA 1T (TP73-AS1) is a newly discovered lncRNA involved in the occurrence and development of several cancers. However, its role in lung cancer has not been well investigated yet.
Methods:
The expressions of TP73-AS1, microRNA-27b-3p (miR-27b-3p) and lysosomal-associated protein transmembrane-4 Beta (LAPTM4B) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The cell proliferation, apoptosis, migration and invasion were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Annexin V-FITC/PI and transwell assays, respectively. Tumor xenografts were applied to explore the role of TP73-AS1 in vivo. The target relationship was predicted by StarBase v.2.0 or TargetScan and confirmed by luciferase reporter assay. Pearson's coefficient assay was applied to assess the expression correlation between two groups. Protein expression levels were detected by Western blot.
Results:
We found that TP73-AS1 was strikingly up-regulated in lung cancer tissues and cells. TP73-AS1 depletion inhibited the growth and metastasis of lung cancer cells in vitro. Furthermore, TP73-AS1 could act as an endogenous sponge by directly binding miR-27b-3p, and a notable inverse correlation between them was also discovered. Importantly, knockdown of miR-27b-3p could reverse the inhibitory effects of TP73-AS1 depletion on the growth and metastasis of lung cancer cells. Besides, LAPTM4B was directly targeted by miR-27b-3p and could be co-regulated by TP73-AS1 and miR-27b-3p in lung cancer cells. Silencing TP73-AS1 hampered tumor growth by regulating miR-27b-3p/LAPTM4B axis in vivo.
Conclusion:
TP73-AS1 promoted the progression of lung cancer through regulating miR-27b-3p/LAPTM4B axis and it might be a potential target for diagnosis and treatment of lung cancer.
Insights
Long non-coding RNA TP73-AS1 promotes lung cancer progression by regulating the miR-27b-3p/LAPTM4B axis. This finding suggests TP73-AS1 as a potential diagnostic and therapeutic target for lung cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cancer development.
- The specific function of TP73 antisense RNA 1T (TP73-AS1) in lung cancer remains largely unexplored.
Purpose of the Study:
- To investigate the role of TP73-AS1 in lung cancer progression.
- To elucidate the molecular mechanism underlying TP73-AS1's function in lung cancer, including its interaction with microRNA-27b-3p (miR-27b-3p) and lysosomal-associated protein transmembrane-4 Beta (LAPTM4B).
Main Methods:
- Quantitative real-time polymerase chain reaction (qRT-PCR) to measure gene expression.
- Cellular assays (MTT, Annexin V-FITC/PI, Transwell) to assess proliferation, apoptosis, migration, and invasion.
- In vivo tumor xenograft models.
- Luciferase reporter assays to confirm molecular interactions.
- Western blot analysis for protein expression.
Main Results:
- TP73-AS1 expression was significantly upregulated in lung cancer tissues and cells.
- TP73-AS1 depletion inhibited lung cancer cell growth and metastasis in vitro and tumor growth in vivo.
- TP73-AS1 functions as an endogenous sponge for miR-27b-3p, with an inverse correlation observed between their expression.
- miR-27b-3p directly targets LAPTM4B, and this axis is co-regulated by TP73-AS1.
Conclusions:
- TP73-AS1 promotes lung cancer progression via the miR-27b-3p/LAPTM4B regulatory axis.
- TP73-AS1 represents a potential biomarker for lung cancer diagnosis and a therapeutic target.
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