Abstract: Objective To investigate the effect of long non-coding RNA potassium voltage-gated channel subfamily Q member 1 reverse transcript 1 (lncRNA KCNQ1OT1) on cardiomyocyte proliferation and apoptosis by regulating miR-384/calcium channel, L type, alpha 1C subunit gene(CACNA1C) axis.Methods Real-time quantitative PCR (qRT-PCR) and Western blot were used to detect the protein expression of KCNQ1OT1, miR-384, and CACNA1C in normal cultured rat myocardial H9c2 and CP-R073 cells and in H9c2 and CP-R073 cells induced by hypoxia/reoxygenation (H/R). H9c2 cells were divided into the following groups: a Ct group, a Model group, a si-NC group, a si-KCNQ1OT1 group, a mimic NC group, a miR-384 mimic group, a si-KCNQ1OT1+inhibitor NC group, and a si-KCNQ1OT1+miR-384 inhibitor group.Except for the Ct group, H9c2 cells in other groups were transfected with the corresponding substances to construct a H/R injury model. Furthermore, qRT-PCR was applied to detect the expression of KCNQ1OT1 and miR-384 in cells. The CCK-8 assay and EdU staining were used to detect cell proliferation. Flow cytometry was used to detect apoptosis. ELISA method was used to detect the levels of myoglobin (Mb) and cardiac troponin-Ⅰ (cTnⅠ). Western blot was used to detect the protein expression of CACNA1C, proliferating cell nuclear antigen (PCNA), cysteine-containing aspartate-specific proteases-3 (Caspase-3), Bcl-2-associated X protein (Bax). Dual-luciferase reporter gene assay was used to verify the relationship between KCNQ1OT1 and miR-384, and between miR-384 and CACNA1C.Results The protein expression of KCNQ1OT1 and CACNA1C in H/R-induced H9c2 and CP-R073 cells increased, and the expression of miR-384 decreased, and H/R-induced H9c2 cells had the highest protein expression of KCNQ1OT1 and CACNA1C, and the lowest expression of miR-384. Therefore, H9c2 cells were selected for the subsequent studies.Compared with the Ct group, the Model group showed increases in the expression of KCNQ1OT1, apoptotic rate, the levels of Mb and cTnⅠ, and the expression of CACNA1C, Caspase-3 and Bax, and decreases in the expression of miR-384, D₄₅₀ value, EdU positive rate, and the protein expression of PCNA (P<0.05). Silencing KCNQ1OT1 or overexpressing miR-384promoted H/R-induced H9c2 cell proliferation and inhibited cell apoptosis. Moreover, miR-384 inhibitor attenuated the promoting effects of KCNQ1OT1 silencing on H/R-induced H9c2 cell proliferation and the inhibitory effect on apoptosis. KCNQ1OT1 targeted and regulated the miR-384/CACNA1 C axis.Conclusions Silencing KCNQ1OT1 may inhibit the expression of CACNA1C by up-regulating miR-384, thereby promoting H/R-induced H9c2 cell proliferation and inhibiting cell apoptosis.