Background Circular RNAs (circRNAs) are important regulators of the development and progression of non-small-cell lung cancer (NSCLC) and many other malignancies. The functional importance of circ_0009043 in NSCLC, however, has yet to be established. Methods The expression of circ_0009043, miR-148a-3p, and DnaJ heat shock protein family (Hsp40) member B4 (DNAJB4) in NSCLC cells was assessed via qPCR. The proliferative activity of these cells was examined through EdU uptake and CCK-8 assays, while flow cytometry approaches were used to examine apoptotic cell death rates. Protein expression was measured through Western immunoblotting. Interactions between miR-148a-3p and circ_0009043 or DNAJB4 were detected through RNA immunoprecipitation (RIP) and dual-luciferase reporter assays. The in vivo importance of circ_0009043 as a regulator of oncogenic activity was assessed using murine xenograft models. Results Both NSCLC cells and tissue samples were found to exhibit circ_0009043 upregulation, and lower circ_0009043 expression levels were found to be related to poorer NSCLC patient overall survival. Knocking down circ_0009043 resulted in the enhancement of NSCLC cell proliferative activity and the suppression of apoptotic tumor cell death in vitro, while also driving more rapid in vivo tumorigenesis. Mechanistically, circ_0009043 was found to function as a molecular sponge that sequestered miR-148a-3p, which was in turn able to directly suppress DNAJB4 expression. When miR-148a-3p was overexpressed, this reversed the impact of knocking down circ_0009043 on the apoptotic death and proliferation of NSCLC cells. Conversely, miR-148a-3p inhibition resulted in the suppression of NSCLC cell apoptosis and the enhancement of tumor cell growth, while the downregulation of DNAJB4 reversed these changes. Conclusion Circ_0009043 acts as a tumor suppressor in NSCLC cells, promoting DNAJB4 upregulation via the sequestration of miR-148a-3p.

Background Cisplatin (DDP) is among the most widely used chemotherapeutic drugs for non-small cell lung cancer (NSCLC), yet the frequent emergence of chemoresistance serves as a major barrier to the treatment of this tumor type. Long non-coding RNAs (lncRNAs) have recently been shown to influence the ability of cells to resist particular chemotherapy drugs. The present study was developed to explore the role of the lncRNA SNHG7 as a regulator of NSCLC cell chemosensitivity. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to measure SNHG7 expression in NSCLC tissues from patients that were sensitive/resistant to DDP, correlations between SNHG7 expression levels and the patients’ clinicopathological characteristics were assessed, and the prognostic relevance of SNHG7 expression was examined via the Kaplan-Meier approach. In addition, SNHG7 expression was assessed in NSCLC cell lines that were DDP-sensitive or -resistant, while western blotting and immunofluorescence staining were employed to detect autophagy-associated protein expression in A549, A549/DDP, HCC827, and HCC827/DDP cells. NSCLC cell chemoresistance was quantified via the Cell Counting Kit-8 (CCK-8) assay approach, and flow cytometry was used to detect the apoptotic death of these tumor cells. The chemosensitivity of xenograft tumors in vivo was further assessed to validate the functional importance of SNHG7 as a regulator of NSCLC DDP resistance. Results Relative to paracancerous tissues, NSCLC tumors exhibited SNHG7 upregulation, and this lncRNA was further upregulated in DDP-resistant patients compared to chemosensitive patients. Consistently, higher SNHG7 expression levels were correlated with worse patient survival outcomes. DDP-resistant NSCLC cells were also found to exhibit higher levels of SNHG7 expression than chemosensitive cells, and knocking down this lncRNA enhanced the sensitivity of these cells to DDP treatment, resulting in impaired proliferation and higher rates of apoptotic death. Knocking down SNHG7 was also sufficient to suppress microtubule associated protein 1 light chain 3 beta (LC3B) and Beclin1 protein levels and promote p62 upregulation in vitro . The silencing of this lncRNA additionally inhibited the resistance of NSCLC xenograft tumors to DDP treatment in vivo. Conclusions SNHG7 can promote malignant behaviors and DDP resistance in NSCLC cells at least partly via the induction of autophagic activity.