LncRNA SNHG7 promotes non-small cell lung cancer progression and cisplatin resistance by inducing autophagic activity

Abstract

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.

The role of LncRNA-mediated autophagy in cancer progression

“…In NSCLC, the lncRNA LUCAT1 improves resistance to DDP chemotherapy and stimulates autophagy and metastasis of NSCLC cells via targeting the miR-514a-3p/ULK1 axis ( Shen et al, 2020 ). In addition, the upregulated lncRNA SNHG7 promotes NSCLC progression and resistance to DDP by the induction of autophagy activity through the modulation of LC3B and BECN1 ( She et al, 2023 ). In ovarian cancer, elimination of autophagy mediated by DIRAS3 and ULK1 via the lncRNA RNF157-AS1 reduced the resistance of ovarian cancer cell resistance to DDP ( Yang et al, 2022 ).…”

Long noncoding RNA POU6F2-AS2 contributes to the aggressiveness of nonsmall-cell lung cancer via microRNA-125b-5p-mediated E2F3 upregulation

“…Reportedly, NSCLC involves the aberrant expression of several lncRNAs, and their dysregulation contributes to the oncogenesis of NSCLC [12][13][14]. For instance, an lncRNA named SNHG7 aggravates the malignancy and promotes the cisplatin resistance of NSCLC [15]. Furthermore, the ablation of the lncRNA DLGAP1-AS1 decreases the cell viability and motility of NSCLC cells and promotes their apoptosis [16].…”

Identification and Validation of a m5c-related lncrna signature predict prognosis and immune response of clear cell renal cell carcinoma

“…LncRNA CACClnc could be used as a predictor of the e cacy of chemotherapy in patients with colorectal cancer [18]. LncRNA SNHG7 could promote disease progression and drug resistance by inducing autophagy activity in non-small cell lung cancer [19]. However, the role of LncRNAs in ccRCC needs to be further studied.…”