H19 contributes to poor clinical features in NSCLC patients and leads to enhanced invasion in A549 cells through regulating miRNA‑203‑mediated epithelial‑mesenchymal transition

Abstract

Recent studies have demonstrated that the overexpression of H19 may contribute towards development of tumorigenesis in various types of cancer. To investigate the role of H19 in the development of non-small cell lung cancer (NSCLC), 76 NSCLC tissues samples and their adjacent normal tissue samples were collected. Expression level of H19, and its association with clinicopathological features and overall survival was analyzed. It was found that compared with normal adjacent tissues, H19 expression was elevated in NSCLC tissues along with a decreased miR-203 expression level. It was also found that patients who were in advanced clinical stages had a higher H19 and a lower miR-203 expression compared to normal tissues. The overall survival time of patients with higher H19 expression was shorter compared with the lower H19 expression group. Upregulation of A549 enhanced cell proliferation and promoted invasion. Overexpression of H19 stimulated the epithelial-mesenchymal transition (EMT) process in lung cancer cells and demonstrated typical morphological characteristics of EMT. The level of mesenchymal marker protein, such as Vimentin and SNAI1 increased; while CDH1 protein level decreased. Also, H19 negatively regulated miR-203. Inhibition of H19 attenuated miR-203 induced EMT process. Upregulation of H19 contributes to poor clinical features in patients with NSCLC, induces occurrence of EMT, promotes proliferation and stimulates cell invasion in NSCLC cell line through regulating miRNA-203 mediated EMT.

Long Non-Coding RNA in the Pathogenesis of Cancers

“…Studies have revealed that the expression of H19 is significantly increased in LC tissues when compared with that in adjacent tissues [40,66]. H19 overexpression is associated with carcinogenesis from early stages to metastasis, reduced disease-free survival (DFS) time, and poor prognosis in LC [4,41,46,67].…”

“…Zhao et al indicated that the overexpression of H19 sponged and inhibited miR-200a function to upregulate zinc finger E-box binding homeobox 1 (ZEB1) and zinc finger E-box binding homeobox 2 (ZEB2), thereby promoting proliferation, migration, invasion, and EMT in LC [40]. It has been demonstrated that upregulation of H19 can induce cell proliferation, invasion, and EMT occurrence by acting as an miRNA sponge and regulating miRNA-203-mediated EMT [66]. Additionally, H19 can induce cell proliferation by promoting the expression of pro-oncogene lin-28 homolog B (LIN28B) via the inhibition of miR-196b expression in A549 and H1299 LC cell lines [71].…”

“…H19 also promotes NSCLC metastasis by activating some cellular signaling pathway proteins, including metastasis associated in colon cancer 1 (MACC1), epidermal growth factor receptor (EGFR), β-catenin, and extracellular-signal-regulated kinase 1/2 (ERK1/2) [64]. Overexpression of H19 promotes cell proliferation, migration, and invasion by upregulating the expression of EMT markers, including snail family transcriptional repressor 1 (SNAI1), N-cadherin, and Vimentin [42,63,64,66,74]. Moreover, upregulation of H19 can induce A549 cells resistance to DDP [74,75].…”

Aquaporin 5 promotes tumor migration and angiogenesis in non‑small cell lung cancer cell line H1299

“…Lung-cancer treatment is promising if the disease is detected at its early stage, and less beneficial at advanced stage, though a relatively high risk of recurrence occurs even after exposure to available potent treatment (3). NSCLC migration and invasion contribute to poor treatment outcome and lung-cancer mortality (4). NSCLC cells aggressively proliferate and invade adjacent tissues, cross the basement membrane and migrate to establish colonies in distant organs of the body via either the vascular system or the lymphatic system (5).…”

lncRNA-CYTOR Works as an Oncogene Through the CYTOR/miR-3679-5p/MACC1 Axis in Colorectal Cancer

“…Rani et al (2016) proved that lncRNA-LnND was significantly downregulated in neuroblastoma by participating in miRNA-mediated regulation of Notch signaling. Ge et al (2018) declared that high-H19 expression greatly promoted cells proliferation, invasion, and contributed to poor clinical features in patients with nonsmall cell lung cancer through regulating miRNA-203-mediated epithelial-mesenchymal transition. The result of bioinformatic analysis showed that lncRNA-CYTOR mainly located in cytoplasm in a variety of cancer cell lines 5 (Fig.…”