The multifaceted role of TMEM16A in cancer

The calcium-activated chloride channel TMEM16A is intimately linked to cancers. Over decades, TMEM16A over-expression and contribution to prognosis have been widely studied for multiple cancers strengthening the idea that TMEM16A could be a valuable biomarker and a promising therapeutic target. Surprisingly, from the survey of the literature, it appears that TMEM16A has been involved in multiple cancer-related functions and a large number of molecular targets of TMEM16A have been proposed. Thus, TMEM16A appears to be an ion channel with a multifaceted role in cancers.In this review, we summarize the latest development regarding TMEM16A contribution to cancers. We will survey TMEM16A contribution in cancer prognosis, the origins of its over-expression in cancer cells, the multiple biological functions and molecular pathways regulated by TMEM16A. Then, we will consider the question regarding the molecular mechanism of TMEM16A in cancers and the possible basis for the multifaceted role of TMEM16A in cancers.     

COPB2 is up‐regulated in breast cancer and plays a vital role in the metastasis via N‐cadherin and Vimentin

Breast cancer (BC) is a common malignant tumour for the adult female and its relative incidence has increased continuously in recent years. The primary molecular mechanisms of breast tumourigenesis remain unclear. With the sequencing technology, we found that coatomer protein complex subunit beta 2 (COPB2) gene is overexpressed in breast cancer tissues. However, the biological function of COPB2 in BC has yet to be determined. This current research demonstrates, significant up‐regulation of COPB2 in tissues of breast cancer while comparing the adjacent normal tissue both invalidated cohort and TCGA cohort. Up‐regulated expression of COPB2 was correlated with lymph node metastasis (LNM) and oestrogen receptor (ER) in the TCGA cohort and a high level of COPB2 was associated with age and lymph node metastasis in the validated cohort. Besides, logistic analysis illustrated in BC patient COPB2 expression, tumour size, age, ER and disease stage were independent high‐risk factors of LNM. Loss of function experiments revealed that down‐regulation of COPB2 could inhibit capacities of proliferation and cell invasion in MDA‐MB‐231 and BT‐549 cell lines. Moreover, underexpression of COPB2 could decrease the EMT‐related protein N‐cadherin and vimentin which may lead to cell invasion. This current research provides new shreds of evidence that COPB2 overexpression shows significant character in the progression of breast cancer. To best of our knowledge, our findings indicated that COPB2 was vital oncogene which was associated with breast cancer.     

Proteomic screen with the proto-oncogene beta-catenin identifies interaction with Golgi coatomer complex I

Beta-catenin is well-known as a key effector of Wnt signalling and aberrant expression is associated with several human cancers. Stabilisation of and atypical subcellular localisation of beta-catenin, regulated in part through specific protein-protein interactions has been linked to cancer development, however the mechanisms behind these pathologies is yet to be fully elucidated. Affinity purification and mass spectrometry were used to identify potential β-catenin interacting proteins in SW480 colon cancer cells. Recombinant β-catenin constructs were used to co-isolate interacting proteins from stable isotope labelled cells followed by detection using mass spectrometry. Several known and new putative interactors were observed. In particular, we identified interaction with a set of coatomer complex I subunits implicated in retrograde transport at the Golgi, and confirmed endogenous interaction of β-catenin with coatomer subunit COPB using immunoprecipitation assays and immunofluorescence microscopy. These observations suggest a hitherto unrecognised role for β-catenin in the secretory pathway and warrant further functional studies to unravel its activity at this cellular location.     

MiR-216a-3p regulates the proliferation,apoptosis, migration,and invasion of lung cancer cells via targeting COPB2

ABSTRACT

Effect of miR-216a-3p on lung cancer hasn’t been investigated. Here, we explored its effects on lung cancer. MiR-216a-3p expression in lung cancer tissues and cells was detected by RT-qPCR. The target gene of miR-216a-3p was predicted by bioinformatics and confirmed by luciferase-reporter assay. After transfection, cell viability, migration, invasion, proliferation, and apoptosis were detected by MTT, scratch, transwell, colony formation, and flow cytometry. The expressions of COPB2 and apoptosis-related factors were detected by RT-qPCR or western blot. MiR-216a-3p was low-expressed and COPB2 was high-expressed in lung cancer tissues and cells. MiR-216a-3p targeted COPB2 and regulated its expression. MiR-216a-3p inhibited lung cancer cell viability, migration, invasion, and proliferation, while promoted apoptosis. Effect of miR-216a-3p on lung cancer was reversed by COPB2. MiR-216a-3p regulated proliferation, apoptosis, migration, and invasion of lung cancer cells via targeting COPB2.