Objective To investigate the effect of long non⁃coding RNA (lncRNA) AC092718.4 on drug resistance of breast cancer in human epidermal growth factor receptor 2 (HER2) positive and its possible mechanism. Methods (1) Breast cancerous tissues from breast cancer patients with trastuzumab non⁃drug resistance and drug resistance in HER2 positive were obtained (setting as the non⁃drug resistance group or the drug resistance group), and their mRNA and protein expressions of lncRNA AC092718.4, miR⁃135a⁃5p, and S100 calcium binding protein P (S100P) were detected. (2) Regarding HER2⁃positive breast cancerous cell line MDA⁃MB⁃361 cells, which were insensitive to trastuzumab, as primary drug resistant cell model, and regarding breast cancerous cell strain BT⁃474 cells as parent, the cell model of secondary drug resistance on trastuzumab (BT⁃474/TRA cells) was established. The expressions of lncRNA AC092718.4, miR⁃135a⁃5p, and S100P mRNA and protein of the three categories of cells were detected. After 48⁃hour intervention of trastuzumab in the same concentration, activity of the three categories of cells was detected. (3) MDA⁃MB⁃361 cells were obtained and assigned to sh⁃AC092718.4 group, sh⁃NC group, or control group for experiment, therein cells in the sh⁃AC092718.4 group and the sh⁃NC group were transfected with sh⁃AC092718.4 and sh⁃NC, respectively, whereas cells in the control group did not receive treatment. After 48⁃hour intervention of trastuzumab in the same concentration, activity of cells in the three groups were detected. (4) The starBase and TargetScan were used to predict potential targets of lncRNA AC092718.4 and miR⁃135a⁃5p, respectively. The dual luciferase reporter gene experiment was used to validate the targeted binding between lncRNA AC092718.4 and miR⁃135a⁃5p, and between miR⁃135a⁃5p and S100P. Results (1) Compared with the non⁃drug resistance group, the drug resistance group exhibited elevated expressions of lncRNA AC092718.4, S100P mRNA, and S100P protein, while a decreased expression of miR⁃135a⁃5p (P<0.05). (2) Compared with BT⁃474 cells, expressions of lncRNA AC092718.4, S100P mRNA, and S100P protein of BT⁃474/TRA cells and MDA⁃MB⁃361 cells were elevated, while miR⁃135a⁃5p expression was decreased, as well as cell activity of trastuzumab was greater after 48 hours of intervention (P<0.05). (3) Compared with the control group and the sh⁃NC group, the sh⁃AC092718.4 group yielded decreased activity of MDA⁃MB⁃361 cells (P<0.05). (4) The results of starBase prediction revealed that lncRNA AC092718.4 had targeted binding loci with miR⁃135a⁃5p; moreover, the results of TargetScan prediction indicated that there were targeted binding loci between miR⁃135a⁃5p and S100P. The results of dual luciferace reporter gene experiment interpreted that lncRNA AC092718.4 might bind directly to miR⁃135a⁃5p, and S100P was the target gene of miR⁃135a⁃5p. Conclusion Breast cancerous cells developing drug resistance on trastuzumab can be promoted by lncRNA AC092718.4. Down⁃regulating lncRNA AC092718.4 expression may relieve MDA⁃MB⁃361 cells on drug resistance of trastuzumab, and its mechanism may be involved lncRNA AC092718.4 as a competitive endogenous RNA competitively binding miR⁃135a⁃5p, thereby up⁃regulating S100P expression.

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