Scientists reveal miR-483-5p mechanisms regulating cancer cell invasion and metastasis

Southern Medical researchers discovered, miR-483-5p can be RhoGDI1 and ALCAM through the target, and promote invasion and metastasis of lung adenocarcinoma.
Scientists reveal miR-483-5p mechanisms regulating cancer cell invasion and metastasis
Southern Medical researchers discovered, miR-483-5p can be RhoGDI1 and ALCAM through the target, and promote invasion and metastasis of lung adenocarcinoma. Related Articles published in the April 7, 2014 in “Cancer Research” magazine.

Tumor metastasis (tumor metastasis), about 90% of all cancer-related deaths reasons. Metastasis is a complex process, through this process, the cancer cells as the place from which the first of the primary tumors, spread to distant parts of the body. Transfer depends on the ability to get two separate – increased motility and invasiveness – of cancer cells. In epithelial – mesenchymal transition (epithelial-mesenchymal transition, EMT) process, epithelial cells lose their polarity, converted into a mesenchymal cell phenotype, is considered crucial in the process of tumor metastasis event. Identify and describe the control EMT, cell motility and invasiveness of molecules, for our understanding of cancer spread is essential. Transfer process of the key regulatory factors including proteins and micrornAs (miRNAs).

WNTs its downstream effector proteins can be adjusted for a variety of cancer development is very important process. Cancer of the Wnt / β-catenin signaling activation, usually drives a transcriptional regulatory program (such as transcriptional regulation of E-cadherin inhibitory factor Snail), which can promote cell migration and invasion. Wnt / β catenin pathway regulatory proteins have been observed abnormalities in various cancers. Recent studies have shown that, WNTs its downstream effector proteins with non-small cell lung cancer (non-small Cell lung carcinoma, NSCLC) bad about and participate in the prognosis of patients with lung metastasis. However, Wnt / β-catenin by what mechanism regulating EMT and tumor metastasis, is not yet fully understood.

Another group of molecules play a key role in the transfer of the miRNA. miRNA functions as 21-24 – mRNAs nucleotide guides, expression regulatory sequences comprising complementary. Studies have demonstrated the role of miRNAs involved in the process of metastasis, including cell proliferation, migration and invasion, EMT. Studies have shown that when miR-10b can be directly involved in the promotion targeting HOXD10 metastatic breast cancer, the relationship between MiRNA was only with the transfer of the first report. Subsequent studies have found, miRNAs also has an inhibitory effect on the transfer, such as increased expression of mir-335 inhibits metastatic invasion of breast cancer cells. Recent studies have demonstrated that several miRNA such as miR-200, miR-205 and miR-221/222 involved in EMT. Given that many miRNAs disorders in cancer, but has not been further studies are expected to become more miRNAs and cancer progression of cancer etiology key factors.

Recently, studies have shown that miR-483 in some cancers disorders, and with poorer disease-specific survival rate. However, the role of miR-483 in lung cancer metastasis, as well as regulation of miR-483 in lung cancer metastasis is still not known.

In this study, the researchers demonstrated, miR-483-5p in human lung adenocarcinoma tumor progression and increases related. miR-483-5p activated by the Wnt / β-catenin signaling, in vitro and in vivo by directly targeting RhoGDI1 (Rho GDP decomposition inhibitor α) and ALCAM (activated leukocyte cell adhesion molecule) recognized both transfer inhibitors promote lung adenocarcinoma cell EMT, invasion and metastasis.

The study also showed that, RhoGDI1 downregulation could enhance the expression of Snail (the most important E-cadherin transcription inhibitor), thus contributing to EMT. Importantly, expression of miR-483-5p and β-catenin levels were positively correlated, but with human lung adenocarcinoma RhoGDI1 and ALCAM levels were negatively correlated. The results of this study identified miR-483-5p as a β-catenin activation before transition miRNA, or transfer inhibitors and ALCAM RhoGDI1 and a negative regulator. In addition, the study of molecular functions of miR-483 and RhoGDI1 and their regulation mechanisms in the transfer, there is provided new insights.

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