MicroRNA-212 functions as a tumor-suppressor in human non-small cell lung cancer by targeting SOX4

Abstract

Increasing evidence has revealed that aberrant expression of miRNAs contributes to non-small cell lung cancer (NSCLC) development and progression. However, the roles and mechanisms of various miRNAs in NSCLC remain to be determined. In the present study, we confirmed that reduced miR-212 expression was present in NSCLC tissues and cell lines. Our clinical analysis revealed that the reduced miR-212 expression was significantly correlated with poor prognostic features including positive lymph node metastasis and advanced tumor-node-metastasis (TNM) stage. Moreover, we demonstrated that miR-212 is a novel independent prognostic marker for predicting 5-year survival of NSCLC patients. The ectopic overexpression of miR-212 inhibited cell migration, invasion and EMT, while downregulated miR-212 reversed the effect. In addition, miR-212 regulated SOX4 by directly binding to its 3'-untranslated region (3'-UTR), leading to suppression of EMT progression. In clinical samples of NSCLC, miR-212 was negatively correlated with SOX4, which was upregulated in NSCLC. Alteration in SOX4 expression reversed the functional effects of miR-212 in regards to migration, invasion and EMT in the NSCLC cells. In conclusion, our data indicated that miR-212 functions as a tumor-suppressor gene by regulating EMT and metastasis of NSCLC by targeting SOX4 signaling, and may represent a novel potential therapeutic target and prognostic marker for NSCLC.

miR‑212 regulated by HIF‑1α promotes the progression of pancreatic cancer

“…miR-212, a cancer-associated miRNA located on chromosome 17p13.3, participates in the progression of different types of human cancer (17). It has been demonstrated that miR-212, as an oncogene, is upregulated in breast cancer (18) and pancreatic cancer (19); and as a suppressor gene, is downregulated in hepatocellular carcinoma (20), prostate cancer (21), non-small cell lung cancer (22) and nasopharyngeal carcinoma (23). Furthermore, aforementioned studies revealed that dysregulated miR-212 has an influence on the progression of a number of solid malignancies.…”

Anticancer effect of HOTTIP regulates human pancreatic cancer via the metabotropic glutamate receptor 1 pathway

“…HOXD10 is another gene that is associated with cancer (30). Although there is no clear difference in HOXD10 expression in cancerous tissues and healthy tissues, the gene has been revealed to be associated with lymphatic metastasis (32). Additionally, HOXD10 expression has been significantly increased in cancer tissues with lymphatic metastases (31).…”

The functions and targets of miR‐212 as a potential biomarker of cancer diagnosis and therapy

“…According to the Table 2, USP9X and SOX4 are the common targets of miR-212-3p or -5p in different tumour types, [84][85][86][87][88][89][90][91] whereas miR-212 may target different genes having different functions in colorectal cancer and NSCLC. 84,88,92,93 Moreover, in cervical cancer, miR-212-3p was reported to play a role of tumour suppressor via targeting SMAD2. 94 Meanwhile, in gastric cancer, miR-212-3p…”