Downregulation of lysyl oxidase‐like 4 LOXL4 by miR‐135a‐5p promotes lung cancer progression in vitro and in vivo

Abstract

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.

miR-135a inhibits malignant proliferation and diffusion of non-small cell lung cancer cells by down-regulating ROCK1 protein

“…Previous studies have reported the clinical value of miR-126 and other miRNA in serum of NSCLC, and they have high applicability for distinguishing smokers with NSCLC from non-NSCLC [11]. miR-135a is a widely used miRNA, which has certain pathophysiological significance in anxiety, endometriosis, lung cancer and other diseases [12][13][14]. According to reports by Shi et al [15], miR-135a is abnormally low in NSCLC cells and tissues, and it can significantly inhibit epithelial-mesenchymal transformation (EMT) and other malignant diffusion behaviors of NSCLC cells.…”

Long Noncoding RNA RAET1K Enhances CCNE1 Expression and Cell Cycle Arrest of Lung Adenocarcinoma Cell by Sponging miRNA-135a-5p

“…Conversely, miR-135a was found to target SIAH1 to promote cell transformation in cervical cancer via the b-catenin pathway (Leung et al, 2014). Furthermore, Zhang et al (2019) reported that miR-135a-5p promoted LC progression via modulating LOXL4 and blockage of LC cells arrested at the G1 phase. The reasons for these findings could be the differences in the samples used for in vivo (LC tissue) vs. in vitro (LC cell lines) studies.…”

LncRNA MBNL1‐AS1 represses cell proliferation and enhances cell apoptosis via targeting miR‐135a‐5p/PHLPP2/FOXO1 axis in bladder cancer

“…As a critical member of miR‐135 family, miR‐135a had been investigated in multiple cancers, and its aberrant expression might be implicated in the development and progression of tumors. For instance, Zhang et al demonstrated that miR‐135a could accelerate cell growth and proliferation of lung cancer, but repress cell apoptosis . In colon adenocarcinoma, miR‐135a was suggested to be a "sponge" of lncRNA FOXD3‐AS1 to regulate cell proliferation, migration, invasion, and apoptosis by targeting SIRT1 .…”