MicroRNA-21 (miR-21) Regulates Cellular Proliferation, Invasion, Migration, and Apoptosis by Targeting PTEN, RECK and Bcl-2 in Lung Squamous Carcinoma, Gejiu City, China

Abstract

BackgroundIn South China (Gejiu City, Yunnan Province), lung cancer incidence and associated mortality rate is the most prevalent and observed forms of cancer. Lung cancer in this area is called Gejiu squamous cell lung carcinoma (GSQCLC). Research has demonstrated that overexpression of miR-21 occurs in many cancers. However, the unique relationship between miR-21 and its target genes in GSQCLC has never been investigated. The molecular mechanism involved in GSQCLC must be compared to other non-small cell lung cancers in order to establish a relation and identify potential therapeutic targets.Methodology/Principal FindingsIn the current study, we initially found overexpression of miR-21 occurring in non-small cell lung cancer (NSCLC) cell lines when compared to the immortalized lung epithelial cell line BEAS-2B. We also demonstrated that high expression of miR-21 could increase tumor cell proliferation, invasion, viability, and migration in GSQCLC cell line (YTMLC-90) and NSCLC cell line (NCI-H157). Additionally, our results revealed that miR-21 could suppress YTMLC-90 and NCI-H157 cell apoptosis through arresting cell-cycle at G2/M phase. Furthermore, we demonstrated that PTEN, RECK and Bcl-2 are common target genes of miR-21 in NSCLC. Finally, our studies showed that down-regulation of miR-21 could lead to a significant increase in PTEN and RECK and decrease in Bcl-2 at the mRNA and protein level in YTMLC-90 and NCI-H157 cell lines. However, we have not observed any remarkable difference in the levels of miR-21 and its targets in YTMLC-90 cells when compared with NCI-H157 cells.Conclusions/SignificancemiR-21 simultaneously regulates multiple programs that enhance cell proliferation, apoptosis and tumor invasiveness by targeting PTEN, RECK and Bcl-2 in GSQCLC. Our results demonstrated that miR-21 may play a vital role in tumorigenesis and progression of lung squamous cell carcinoma and suppression of miR-21 may be a novel approach for the treatment of lung squamous cell carcinoma.

Exosome-shuttling microRNA-21 promotes cell migration and invasion-targeting PDCD4 in esophageal cancer

“…Many studies have been conducted on the function of miR-21 in tumor occurrence and development. These studies showed that miR-21 could promote cell growth, proliferation, invasion and metastasis of various tumor cells by targeting PTEN, PDCD4, RECK, FASL and TIMP3 (38)(39)(40). Hiyoshi et al (41) found that the inhibition of microRNA-21 could lead to a reduction of the proliferation and invasion in esophageal squamous cell carcinoma cell lines by increasing PDCD4 protein expression With paired t-test performed to determine the significant difference.…”

“…PDCD4, a tumor suppressor gene, was demonstrated to have low expression in various tumor tissues and cells (44,45). PDCD4, which was predicted to be a miR-21 target gene by TargetScan, has been reported to be a key regulator of tumor proliferation, apoptosis, adhesion, migration, invasion and metastasis (28)(29)(30)40,46). Tumor invasion is a multistep process in which cell motility is coupled with proteolysis and involves interaction of cells with extracellular matrix (ECM).…”

XRCC1 Gene Polymorphisms and miR-21 Expression in Patients with Colorectal Carcinoma

“…Moreover, several studies have reported an association between XRCC1 Arg/Gln or Gln/Gln genotypes and the clinical response to chemotherapy in colorectal cancer (CRC) [4]. Huang et al [3] is involved in the development of malignant tumors through its effects on cell apoptosis, proliferation, invasion, and metastasis by targeting phosphatase, tensin homolog (PTEN), and tissue inhibitor of metalloproteinases 3 (TIMP3) or through its role in signaling pathways such as Wnt/β-catenin, PTEN/PI-3K/AKT, and RAS/ MEK/ERK [6,7]. Recent studies showed that miR-21 is frequently up-regulated in CRC and that elevated expression of miR-21 is associated with worse prognosis and inefficient response to chemotherapy [8,9].…”

Over-Expression of miR-21 and Lower PTEN Levels in Wilms’ Tumor with Aggressive Behavior

“…The oncogenic activity of miR-21 on biological behavior of tumor cells is mainly by regulating downstream target genes (Xu et al 2014). Downstream target genes of miR-21 that have been experimentally confirmed include PDCD4, RECK, TIMP-3, and TPM1 which are involved in NSCLC, gastric cancer, cervical cancer, and colorectal cancer.…”