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

Kelin She; Shushuai He; Xiao Lu; Shaoqi Yu; Mengna Li; Wei Xiong; Ming Zhou

doi:10.21037/jtd-22-1826

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

J Thorac Dis. 2023 Jan 31;15(1):155-167. doi: 10.21037/jtd-22-1826. Epub 2023 Jan 16.

Authors

Kelin She^{1

2

3}, Shushuai He⁴, Xiao Lu⁴, Shaoqi Yu⁴, Mengna Li^{1

3}, Wei Xiong^{1

3}, Ming Zhou^{1

3}

Affiliations

¹ Cancer Research Institute, Central South University, Changsha, China.
² Department of Thoracic Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China.
³ NHC Key Laboratory of Carcinogenesis, Central South University, Changsha, China.
⁴ Department of Thoracic Surgery, the Central Hospital of Shaoyang Affiliated to University of South China, Shaoyang, China.

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.

Keywords: Non-small cell lung cancer (NSCLC); SNHG7; autophagy; chemoresistance; cisplatin (DDP).