| INTRODUC TI ONAs a member of an integrin family, CD49a is expressed on a variety of immune cells including T cells, natural killer T cells (NKT), and NK cells. CD49a plays important roles in innate and adaptive immunemediated responses as well as in inflammation, regulation of growth, differentiation, 1 and liver cirrhosis. 2,3 CD8 + CD49a + Trm (Tissue-resident memory T cells) cells and CD8 + CD49a − Trm cells exert significantly different immune effects. 4 CD49a also regulates the migration, retention, and preservation of immune cells. Interaction of CD49a with collagen promotes immune cells proliferation and the secretion of inflammatory cytokines, which upregulate the expression of CD49a on endothelial cells and mesangial cells, promoting the formation of blood vessels. 2,3 In normal pregnancy, embryonic trophoblast cells and maternal decidual stromal cells comprise the maternal-fetal interface. NK cells, components of the innate immune system, are concentrated within the decidual tissue of the maternal-fetal interface. 5,6 A recent study has shown integrin, αvβ3, to regulate adhesion between villous trophoblastic cells. When a small molecule inhibitor (SB-273005) was used to inhibit the expression of Problem: The function of CD49a on human decidual natural killer (dNK) cells is unknown. Method of study: The expression of CD49a on dNK cells from human patients with recurrent spontaneous abortions or age-matched healthy controls was analyzed by flow cytometry. DNK cells were treated with CD49a neutralizing antibody and analyzed for function (cytokines production and cytotoxic activity). Long non-coding RNA (lncRNA) microarray analysis was used to identify a potential regulator of CD49a. Results: DNK cells from human patients who underwent recurrent spontaneous abortions had lower levels of CD49a and increased perforin, granzyme B, and IFN-r expression, when compared to dNK cells from age-matched healthy controls. Perforin, granzyme B, and IFN-r expression levels in dNK cells were upregulated, while the migration and adhesion of dNK cells were downregulated by CD49a-neutralizing antibody. By the 51 Cr release assay, the killing activity of dNK cells also increased with CD49a neutralizing antibody. Further, lnc-49a, a newly identified lncRNA, was shown to be a positive regulator of CD49a in primary human NK cells. Conclusion: CD49a is involved in the regulation of dNK cells functions, including cytotoxic activity, migration, and adhesion. Further, lnc-49a is a positive regulator of CD49a in human primary dNK cells. K E Y W O R D S adhesion, CD49a, long non-coding RNAs, migration, natural killer cells S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section at the end of the article. How to cite this article: Li H, Hou Y, Zhang S, et al. CD49a regulates the function of human decidual natural killer cells. Am J Reprod Immunol. 2019;81:e13101. https://doi.

Background: miR-100 has been reported to closely associate with gastric cancer (GC) initiation and progression. However, the underlying mechanism of miR-100-3p in GC is still largely unclear. In this study, we intend to study how miR-100-3p regulates GC malignancy. Methods: The expression levels of miR-100-3p in vitro (GES-1 and GC cell lines) and in vivo (cancerous and normal gastric tissues) were examined by quantitative real-time PCR (qRT-PCR). MTT and PE/Annexin V analyses were responsible for measurement of the effects of miR-100-3p on GC cell proliferation and apoptosis. Transwell assay with or without matrigel was used to examine the capacity of migration and invasion in GC cells. The interaction of miR-100-3p with bone morphogenetic protein receptor 2 (BMPR2) was confirmed through transcriptomics analysis and luciferase reporter assay. qRT-PCR and Western blot analyses were applied to determine the expression of ERK/AKT and Bax/Bcl2/Caspase3, which were responsible for the dysfunction of miR-100-3p. Results: miR-100-3p was down-regulated in GC cell lines and cancerous tissues, and was negatively correlated with BMPR2. Loss of miR-100-3p promoted tumor growth and BMPR2 expression. Consistently, the effects of miR-100-3p inhibition on GC cells were partially neutralized by knockdown of BMPR2. Over-expression of miR-100-3p simultaneously inhibited tumor growth and down-regulated BMPR2 expression. Consistently, over-expression of BMPR2 partially neutralized the effects of miR-100-3p over-expression. Further study demonstrated that BMPR2 mediated the effects downstream of miR-100-3p, which might indirectly regulate ERK/AKT and Bax/Bcl2/Caspase3 signaling pathways. Conclusion: miR-100-3p acted as a tumor-suppressor miRNA that down-regulated BMPR2, which consequently inhibited the ERK/AKT signaling and activated Bax/Bcl2/Caspase3 signaling. This finding provided novel insights into GC and could contribute to identify a new diagnostic and therapeutic target.

Hepatocellular carcinoma (HCC) is an aggressive and challenging disease to treat. Due to the lack of effective early diagnosis and therapy for the illness, it is crucial to identify novel biomarkers that can predict tumor behavior in HCC. In such cases, family with sequence similarity 210 member B (FAM210B) is abundant in various human tissues, but its regulatory mechanisms and role in various tissues remain unclear. In this study, we analyzed the expression pattern of FAM210B in HCC using public gene expression databases and clinical tissue samples. Our results confirmed that FAM210B was dysregulated in both HCC cell lines and HCC paraffin section samples. FAM210B depletion significantly increased the capacity of cells to grow, migrate, and invade in vitro, while overexpression of FAM210B suppressed tumor growth in a xenograft tumor model. Furthermore, we identified FAM210B’s involvement in MAPK signaling and p-AKT signaling pathways, both of which are known oncogenic signaling pathways. In summary, our study provides a rational basis for the further investigation of FAM210B as a valuable biological marker for diagnosing and predicting the prognosis of HCC patients.