Abstract: OBJECTIVE To investigate the effect of long non-coding RNA (LncRNA) plasmacytoma variant translocation 1 (PVT1) targeting miR-9-5p on alveolar epithelial cell injury induced by Streptococcus pneumoniae (Sp). METHODS Human pulmonary alveolar epithelial cells (HPAEpiC) were selected and randomly divided into the following groups: Control group (conventional culture), Sp group (cells infected with Sp at 1×10⁸ CFU/ml), sh-NC group (Sp induction + transfected with sh-NC), sh-PVT1 group (Sp induction + transfected with sh-PVT1), sh-PVT1 + anti-NC group (Sp induction + transfected with sh-PVT1 and anti-NC) and sh-PVT1 + anti-miR-9-5p group (Sp induction + transfected with sh-PVT1 and anti-miR-9-5p). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was employed to detect the expression of LncRNA PVT1 and miR-9-5p in cells. CCK8 assay and colony formation assay were conducted to assess cell proliferation. Apoptosis rate was measured by flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was conducted to determine the expression of inflammatory markers in cells. Protein expression was analyzed via Western blotting. The targeting relationship between LncRNA PVT1 and miR-9-5p was verified by dual-luciferase reporter assay. RESULTS The Sp group exhibited higher levels of LncRNA PVT1 expression, apoptosis rate, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), P21 and Bax protein expression compared to the Control group (P<0.05), while miR-9-5p expression, survival rate, colony count, IL-10 levels and Bcl-2 protein expression were lower (P<0.05). The sh-PVT1 group showed lower LncRNA PVT1 expression, apoptosis rate, TNF-α, IL-6 levels, P21 and Bax protein expression compared to the Sp and sh-NC groups (P<0.05), whereas miR-9-5p expression, survival rate, colony count, IL-10 levels and Bcl-2 protein expression were higher (P<0.05). Compared to the sh-PVT1 and sh-PVT1＋anti-NC groups, the sh-PVT1＋anti-miR-9-5p group demonstrated increased apoptosis rate, TNF-α, IL-6 levels, P21 and Bax protein expression (P<0.05), alongside decreased miR-9-5p expression, survival rate, colony count, IL-10 levels and Bcl-2 protein expression (P<0.05). The PVT1-WT＋miR-9-5p mimic group exhibited significantly lower dual-luciferase activity than the PVT1-WT＋mimic-NC group (P<0.05). CONCLUSION LncRNA PVT1 can target and inhibit miR-9-5p expression, thereby inducing alveolar epithelial cell injury.