Purpose
Non-small cell lung cancer (NSCLC) is a typical epithelial lung cancer with high metastasis, incidence and mortality. In recent years, long noncoding RNA small nucleolar RNA host gene 7 (
SNHG7
) has been identified as significant regulator in different cancer types, including NSCLC. However, the underlying molecular mechanism of
SNHG7
during NSCLC tumorigenesis and progression remains largely unclear.
Methods
SNHG7
and miR-181a-5p expression in NSCLC tumors and cells were detected by qRT-PCR. Cell viability, migration, invasion and apoptosis were evaluated by CCK-8, transwell and flow cytometry assay, respectively. A549 and NCI-H1299 xenograft mice model was constructed by subcutaneously injecting cells stably transfected with sh-SNHG7 and sh-NC. The interaction between
SNHG7
and miR-181a-5p was validated by luciferase reporter system, RIP and RNA pull down assay. Protein expression of cleaved caspase 3, proliferating cell nuclear antigen (PCNA), AKT, p-AKT, mammalian target of rapamycin (mTOR) and p-mTOR was analyzed by Western blot.
Results
SNHG7
expression was up-regulated while miR-181a-5p expression was down-regulated in NSCLC tumors, especially those from patients at Phase III+IV, compared with normal tissues. However,
SNHG7
depletion attenuated tumor growth in vitro and in vivo. Moreover, miR-181a-5p inhibitor abolished
SNHG7
silencing induced inhibition on proliferation, migration and invasion in NSCLC. Subsequently, we found
SNHG7
modulated cell progression by targeting miR-181a-5p and activating AKT/mTOR signaling pathway.
Conclusion
SNHG7 accelerates proliferation, migration and invasion of NSCLC by suppressing miR-181a-5p through AKT/mTOR signaling pathway, thus presenting desirable biomarkers for NSCLC therapy.
Lung cancer is devastating cancer that ranks as the leading cause of cancer-related death. Long noncoding RNA (lncRNA) opioid growth factor receptor pseudogene 1 (OGFRP1) was recognized as an oncogene in many cancers. However, the molecular mechanism of OGFRP1 in lung cancer is still poorly understood. The expression of target RNAs and genes was detected by quantitative real-time PCR and western blot. The interaction between miR-299-3p and OGFRP1 or solute carrier family 38 member 1 (SLC38A1) was predicted by StarbaseV3.0 and verified by dual-luciferase reporter assay and Pearson's correlation coefficient. Besides, a transplantation model of human lung cancer in nude mice was established to evaluate the role of OGFRP1 in lung cancer. OGFRP1 and SLC38A1 were overexpressed, whereas miR-299-3p was lowly expressed in lung cancer tumors and cells. OGFRP1 knockdown suppressed cell proliferation and facilitated ferroptosis by promoting lipid peroxidation and iron accumulation in lung cancer. Besides, Furthermore, miR-299-3p inhibitor or SLC38A1 overexpression attenuated OGFRP1 depletion-induced suppression on cell proliferation and ferroptosis in lung cancer. Animal experiments indicated that OGFRP1 deficiency restrained tumor growth in vivo by regulating the miR-299-3p/ SLC38A1 axis. OGFRP1 regulated cell proliferation and ferroptosis in lung cancer by inhibiting miR-299-3p to enhance SLC38A1 expression, providing a novel therapeutic strategy for lung cancer.
Background
Circular RNAs (circRNAs) are a novel type of endogenous RNAs and play vital roles in lung adenocarcinoma. However, the function and underlying mechanism of circ_0020850 in lung adenocarcinoma remain unknown.
Methods
The levels of circ_0020850, microRNA-326 (miR-326), and Beclin1 (BECN1) were analyzed by real-time quantitative polymerase chain reaction and western blot analyses. The migration and invasion were determined by wound healing and transwell assays, respectively. Colony formation assay was used to assess cell proliferation ability. The angiogenic ability was analyzed by Matrigel angiogenesis assay. The apoptosis rate was calculated by flow cytometry assay. Dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays were conducted to confirm the interaction relationship among circ_0020850, miR-326, and BECN1. A xenograft mice model was established to assess the role of circ_0020850 in vivo.
Results
We found that circ_0020850 was obviously overexpressed in lung adenocarcinoma tissues and cells. Knockdown of circ_0020850 inhibited migration, invasion, proliferation, and angiogenesis but induced apoptosis in lung adenocarcinoma cells in vitro, as well as curbed tumor growth in vivo. MiR-326 was a target of circ_0020850, and knockdown of miR-326 abolished the suppression effect of circ_0020850 on the malignant behaviors of lung adenocarcinoma cells. Additionally, miR-326 could negatively regulate BECN1 expression, thereby regulating lung adenocarcinoma cell phenotypes. Importantly, circ_0020850 could directly bind to miR-326 and thus relieve miR-326-mediated inhibition on BECN1.
Conclusion
Circ_0020850 promoted the malignant development of lung adenocarcinoma by regulating miR-326/BECN1 axis, indicating that circ_0020850 might serve as a promising target for the diagnosis and treatment of lung adenocarcinoma patients.
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