Aberrant microRNAs are widely identified in multiple cancers, including lung cancer. miR‐135a‐5p can function as a significant tumor regulator in diverse cancers via impacting multiple genes in oncogenic pathways. Nevertheless, the biological role of miR‐135a‐5p in lung cancer is poorly known. Here, we investigated its function in lung cancer. As exhibited, miR‐135a‐5p was elevated in lung cancer cells in contrast to BEAS‐2B cells. Then, we inhibited miR‐135a‐5p expression by transfecting LV‐anti‐miR‐135a‐5p into lung cancer cells. As displayed, miR‐135a‐5p was obviously reduced in A549 and H1299 cells. Knockdown of miR‐135a‐5p repressed lung cancer cell growth and cell proliferation. Meanwhile, cell colony formation capacity was depressed, cell apoptosis was enhanced and cell cycle progression was blocked in G1 phase by inhibition of miR‐135a‐5p in vitro. Additionally, the migration and invasion of A549 and H1299 cells was strongly depressed by LV‐anti‐miR‐135a‐5p. For another, by using informatics analysis, lysyl oxidase‐like 4 (LOXL4) was speculated as the downstream target of miR‐135a‐5p. We validated their direct correlation and moreover, overexpression of miR‐135a‐5p restrained LOXL4 levels in lung cancer cells. Subsequently, we proved that miR‐135a‐5p promoted lung cancer development via targeting LOXL4 by carrying out the in vivo assays. Taken these together, our study revealed miR‐135a‐5p might be indicated as a perspective for lung cancer via targeting LOXL4.

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