Transmembrane protein 88 (TMEM88), a newly discovered protein localized on the cell membrane.Recent studies showed that TMEM88 was involved in the regulation of several types of cancer.TMEM88 was expressed at significantly higher levels in breast cancer (BC) cell line than in normal breast cell line with co-localized with Dishevelled (DVL) in the cytoplasm of BC cell line. TMEM88 silencing in the ovarian cancer cell line CP70 resulted in significant upregulation of Wnt downstream genes (c-Myc, cyclin-D1) and other Wnt target genes including JUN, PTIX2, CTNNB1 (β-catenin), further supporting that TMEM88 inhibits canonical Wnt signaling pathway. Wnt signaling pathway has been known to play important roles in many diseases, especially in cancer. For instance, hepatocellular carcinoma (HCC) has become one of the most common tumors harboring mutations in the Wnt signaling pathway. As the inhibitor of Wnt signaling, TMEM88 has been considered to act as an oncogene or a tumor suppressor. Up-regulated TMEM88 or gene therapy approaches could be an effective therapeutic approach against tumor as TMEM88 inhibits Wnt signaling through direct interaction with DVL. Here, we review the current knowledge on the functional role and potential clinical application of TMEM88 in the control of various cancers. HighlightsWnt signaling displays an important role in several pathogenesis of cancer.Wnt signaling pathway is activated during cancer development.TMEM88 has an impact on cancer by inhibiting canonical Wnt signaling.We discuss the importance and new applications of TMEM88 in cancer therapy. K E Y W O R D Sβ-catenin, cancer, cancer therapy, TMEM88, Wnt signalling pathway Abbreviations: 1,25(OH)2D3, 1,25-Dihydroxyvitamin D3; AKT/mTOR, protein kinase B/the mammalian target of rapamycin; ATF2, Activating transcription factor 2; BC, breast cancer; CBE, clinical breast exam; CIZ1b, b-variant form of CIZ1; CK1, casein kinase 1; CRD, cystein-rich domain; CTNNB1, catenin β1; Dnmt3a, DNA (cytosine-5)-methyltransferase 3A; DVL, dishevelled; EMT, epithelial-mesenchymal transition; FAK, focal adhesion kinase; FZD, frizzled; GSK3β, glycogen synthase kinase 3β; HCC, hepatocellular carcinoma; HSCs, hematopoietic stem cells; IDCs, invasive ductal carcinomas; LC, lung cancer; LRP5, low density lipoprotein receptor-related protein-5; METTL13, methyltransferase like 13; MMP-7, matrix metalloproteinase-7; MRI, magnetic resonance imaging; NSCLC, nonsmall cell lung cancer; OC, ovarian cancer; P38, protein 38; PFS, progression-free survival; TCF/LEF, T cell factor/lymphoid enhancer factor; TCGA, the cancer genome atlas; TMEM88, transmembrane protein 88; TNBC, triple-negative breast cancer; VWV, Val-Trp-Val; Zo-1, tight junction protein 1.Yun-xuan Ge, Chang-hui Wang, and Fu-yong Hu have contribute equally to this work.

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During the liver fibrosis recovery stage tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can effectively induce apoptosis of activated hepatic stellate cells (HSCs). Normal hepatic stellate cells are resistant to TRAIL cytotoxicity. Therefore, enhancing the sensitivity of TRAIL-induced apoptosis of HSCs may be useful to treat hepatic fibrogenesis. Here, we demonstrated that miR-145 and TRAIL were down-regulated in both liver fibrosis tissue samples and transforming growth factor-β1 induced HSCs, concomitant with increased the expression of ZEB2. In addition, we found that mimics-mediated over-expression of miR-145 led to resistance to the ZEB2 expression and up-regulation of the TRAIL-induced apoptosis after treatment of LX-2 cells with TRAIL. Furthermore, ZEB2-siRNA transfected LX-2 cells showed the increased sensitivity to TRAIL-induced apoptosis. Whereas, opposite results were obtained in miR-145-inhibitor group or ZEB2 plasmid group. Moreover, miR-145 regulated ZEB2 gene expression by specifically interacting with the 3′-UTR of ZEB2 mRNA to inhibit the expression of ZEB2. Further studies showed that the over-expression of ZEB2 could inhibit TRAIL-induced apoptosis via inhibiting nuclear factor-κB (NF-κB) signaling pathway in LX-2 cells. Collectively, our data suggest that up-regulation of miR-145 can down-regulate ZEB2 expression, consequently promoting TRAIL-induced apoptosis in LX-2 cells through NF-κB signaling pathway, which facilitates the resolution of liver fibrosis.

Recent data have shown that Transmembrane protein 88 (TMEM88), a newly discovered protein localized on the cell membrane, interacts with the PDZ domain of disheveled-1 (Dvl-1) in Xenopus embryos. Indeed, TMEM88 might inhibit the canonical Wnt/β-catenin signaling pathway by competing with LRP5/6 for interaction with Dvl-1. TMEM88 plays a crucial role in regulating human stem cell differentiation and embryonic development. Until recently, the function of TMEM88 has been a matter of debate. In this study, we explore the role of TMEM88 in cytokine secretion and the role of the MAPK and Wnt/β-catenin signaling pathway in tumor necrosis factor-alpha (TNF-α)-induced TMEM88 expression in LX-2 cells. We demonstrated that overexpression of TMEM88 results in an upregulation of IL-6 and IL-1β secretion. On the other hand, knockdown of TMEM88 by transfecting siRNA decreased IL-6 and IL-1β secretion in LX-2 cells. Meanwhile, the results showed that TMEM88 silencing could increase the expression levels of canonical Wnt/β-catenin accompanied with upregulated phosphorylation of wnt3a, wnt10b and β-catenin protein levels in response to TNF-α. In conclusion, these results indicated that TMEM88 plays a significant role in TNF-α-enhanced cytokine (IL-6 and IL-1β) secretion of LX-2 cells via regulating JNK/P38 and canonical Wnt/β-catenin signaling pathway.

In this work, porous polycaprolactone (PCL) scaffolds were designed and fabricated using selective laser sintering (SLS). The critical processing parameters of the SLS for PCL were optimised. This work post-processed these PCL scaffolds to produce PCL/alginate/ polyacrylamide (PAAm) scaffolds to improve their performance. The experiment mechanical property assessment showed that the sample's average elastic modulus increases from 6.99 MPa (PCL) to 12.67 MPa (PCL/alginate/PAAm), and the elongation at break of samples increases from 59% (PCL) to 112.9% (PCL/alginate/PAAm). Cell seeding and in vitro culture showed that cell viability remained above 94% over 5 days. Thus, the current study suggests that a promising strategy for the improvement of the characteristics of PCL/alginate/PAAm scaffolds and advances the potential application of SLS technique towards skeletal tissue repair.