Natural Antisense Long Noncoding RNA HHIP-AS1 Suppresses Non-Small-Cell Lung Cancer Progression by Increasing HHIP
Yan Yang1, Yue Cheng2, Yanfei Mou2
1Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Department of Medical Oncology, Chongqing University Cancer Hospital, Chongqing 400030, China.
Abstract:
Non-small-cell lung cancer (NSCLC) is a major category of lung cancer, with high incidence and high mortality. Natural antisense long noncoding RNAs (lncRNAs) are involved in the development of NSCLC via their regulation of biological processes. However, the function of the lncRNA Hedgehog-interacting protein antisense RNA 1 (HHIP-AS1) in NSCLC is mostly unknown. In the study discussed here, HHIP-AS1 and HHIP levels were predicted based on the TCGA database, and detected via qRT-PCR or western blotting assays. Cell proliferation, migration, and invasion were measured via CCK-8 and trans-well assays. Related protein levels were measured using western blotting analysis. The results showed that HHIP-AS1 and HHIP levels are downregulated in NSCLC, and that low HHIP-AS1 and HHIP expression is associated with poor outcomes. HHIP-AS1 overexpression represses cell proliferation, migration, and invasion in NSCLC. HHIP-AS1 enhances HHIP expression and stability, and this effect is mediated by CELF2. HHIP silencing attenuates the suppressive roles of HHIP-AS1 in proliferation, migration, and invasion. As a result of these findings, it is concluded that HHIP-AS1 overexpression restrains proliferation, migration, and invasion of NSCLC cells by increasing HHIP stability via its targeting of CELF2.
Insights
Hedgehog-interacting protein antisense RNA 1 (HHIP-AS1) is downregulated in non-small-cell lung cancer (NSCLC). Overexpression of HHIP-AS1 inhibits NSCLC cell proliferation, migration, and invasion by stabilizing HHIP protein levels.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Non-small-cell lung cancer (NSCLC) presents high incidence and mortality rates.
- Long noncoding RNAs (lncRNAs) are implicated in NSCLC development.
- The role of Hedgehog-interacting protein antisense RNA 1 (HHIP-AS1) in NSCLC remains largely uncharacterized.
Purpose of the Study:
- To investigate the function of HHIP-AS1 in non-small-cell lung cancer.
- To explore the molecular mechanism underlying HHIP-AS1's role in NSCLC progression.
Main Methods:
- TCGA database analysis for HHIP-AS1 and HHIP expression prediction.
- qRT-PCR and Western blotting for expression detection.
- Cell proliferation, migration, and invasion assays (CCK-8, trans-well).
Main Results:
- HHIP-AS1 and HHIP expression are downregulated in NSCLC, correlating with poor prognosis.
- Overexpression of HHIP-AS1 suppresses NSCLC cell proliferation, migration, and invasion.
- HHIP-AS1 enhances HHIP expression and stability through CELF2 interaction.
Conclusions:
- HHIP-AS1 acts as a tumor suppressor in NSCLC.
- HHIP-AS1 restrains NSCLC cell proliferation, migration, and invasion by stabilizing HHIP via CELF2.
- HHIP-AS1 represents a potential therapeutic target for NSCLC.
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