Accumulating evidence has indicated that long noncoding RNAs (lncRNAs) play pivotal roles in the processes of cancer occurrence, progression, and treatment. FAM83A-AS1 is a novel onco-lncRNA involved in various cancers. Nevertheless, the biological function and underlying mechanism of FAM83A-AS1 in lung adenocarcinoma (LUAD) remain largely unclear. In this study, we found FAM83A-AS1 to be upregulated in LUAD tissues and closely associated with tumor size, lymph node metastasis, and TNM stage. In addition, high FAM83A-AS1 expression correlated positively with a poor prognosis. Functional investigation revealed that FAM83A-AS1 promotes LUAD cell proliferation, migration, invasion and the epithelial-mesenchymal transition (EMT) in vitro and tumor growth in vivo. Mechanistically, FAM83A-AS1 functions as an endogenous sponge of miR-150-5p by directly targeting it, removing inhibition of MMP14, a target of miR-150-5p. Furthermore, rescue assays demonstrated that FAM83A-AS1 enhances cell migration, invasion and EMT by modulating the miR-150-5p/MMP14 pathway. Collectively, we conclude that the novel FAM83A-AS1/miR-150-5p/MMP14 axis regulates LUAD progression, suggesting an innovative therapeutic strategy for this cancer.

Objectives: Breast cancer stem‐like cells (BrCSCs) are the major reason for tumour generation, resistance and recurrence. The turbulence of their self‐renewal ability could help to constrain the stem cell expansion. The way BrCSCs divided was related to their self‐renewal capacity, and the symmetric division contributed to a higher ability. Non‐coding long RNA of H19 was involved in multiple malignant procedures; the role and mechanistic proof of non‐coding long RNA of H19 in controlling the divisions of BrCSCs were barely known.Materials and Methods: Indicative functions of H19 in preclinical study were analysed by using the TCGA data base. Division manners were defined by using fluorescence staining.Results: We identified the stimulation of H19 on symmetric division of BrCSCs, which subsequently resulted in self‐renewing increasing. H19 inhibited the Let‐7c availability by acting as its specific molecular sponge, and with Let‐7c inhibition, oestrogen receptor activated Wnt signalling was unconstrained. Similarly, restoring Let‐7c constrained oestrogen receptor activated Wnt factors, which sequentially inhibited the H19 decreasing of Let‐7 bioavailability. Let‐7c is reactivated in vitro where H19 was knockdown, and later inhibited the symmetric division of BrCSCs. Reciprocally, Wnt pathway activation leads to H19 increasing, which in turn decreased Let‐7c bioavailability.Conclusions: Our results revealed a previously undescribed double negative feedback loop between sponge H19 and targeted Let‐7c through oestrogen activated Wnt signalling that dominated in stem cells’ division.

MiR-146a could stimulate tumor growth or block tumor proliferation in systemic malignancies, referring to the specific downstream targeted gene. However, its roles in breast cancer stem-like cells (BrCSCs) are barely known. To dig out its mechanistic functions, we explored the indicative roles of miR-146 in preclinical study, regardless of the hormone receptor status, and the positive correlation between miR-146 and better prognosis was proved, as its correlation to Let-7c was. To uncover the implicated mechanisms, we first identified the suppressive role of miR-146a in stem cells’ renewal, which was achieved by promoting the asymmetric division of BrCSCs. Let-7c was previously revealed with its suppressive functions in stem-like cells expansion, and miR-146 was predicated and successfully proved to bind to and degrade the 3’UTR of LIN28, a maturation blocker of Let-7 family. Results further showed that miR-146a increased the Let-7c level through degrading LIN28, and LIN28 inhibition is required for miR-146a induction of asymmetric stem cells’ division. Moreover, Let-7 controlled Wnt signaling pathway activity could be strengthened due to the miR146 inhibition of H19, later of which was often activated in stem cells group with functional existence of Wnt signaling. H19 itself in turn formed the positive feedback regulation with Let-7. Our results suggested the miR-146a/LIN28/Wnt signaling circle in restraining the symmetric cells division, which was specifically referred to the controlling of the small circle of Let-7c and H19, and together, this dual axis could help to prohibit the stem cells expansion.

Lung carcinoma tops the categories of cancer related motility, and has been treated as the main threat to human health. The functions and related mechanism of FBXW7 controlled lung cancer stem cells' signatures is barely unknown, and the miR-367 regulations of FBXW7 via Wnt signaling have not been explored. Cancer stem cells of either ALDH1+ or CD133+ phenotype were found to be referred to advanced stages in patients with NSCLC (non-small cell lung carcinoma). To study the roles of miR-367, we found greater miR-367 level or FBXW7 level was reserved in NSCLC than that of paired adjacent normal tissues, and their upregulations were positively correlated with Wnt signaling activation. On the contrary, increased miR-367 was correlated with Let-7 repression. MiR-367 was related to stronger sphere forming ability in stem cells of NSCLC. We then explored the functions of the endogenous miR-367 in stem-like cells isolated from NSCLC cell lines. In HEK-293 cells, we identified FBXW7 as the direct downstream gene of miR-367, which consequently released the LIN-28 dependent inhibition of suppressive Let-7. Through informatics analysis, miR-367 was predicated to function through Wnt signaling, and decreased Let-7 played the pivotal role to maintain TCF-4/Wnt pathway activity. The reintroduction of FBXW7 abolished the oncogenic stimulation of miR-367 on TCF-4 activity, with Wnt signaling factors depression. In conclusion, our findings demonstrated the oncogenic roles of miR-367 exerting on the self-renewal ability of cancer stem-like cells through degrading the suppressive FBXW7, eventually helping to maintain Wnt signaling activation through a LIN28B/Let-7 dependent manner.

// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Guodong Xiao1, *, Xiang Li1, *, Gang Li1, *, Boxiang Zhang1, Chongwen Xu2, Sida Qin1, Ning Du1, Jichang Wang3, Shou-Ching Tang4, 5, Jing Zhang1, Hong Ren1, Ke Chen6 and Xin Sun1 1Department of Thoracic Surgery and Oncology, The Second Department of Thoracic Surgery, Cancer Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, 710061, China 2Department of Otorhinolaryngology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, 710061, China 3Department of Vascular and Endovascular Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi’an, Shaanxi Province, 710061, China 4Breast Cancer Program and Interdisciplinary Translational Research Team, Georgia Regents University Cancer Center, Augusta, Georgia, 30912, United States 5Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China 6Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430022, China *These authors are considereds as co-first authors Correspondence to: Xin Sun, email: endeavour.sun@gmail.com Ke Chen, email: shenke@hust.edu.cn Keywords: miR-129, ESR1, DICER1, Let-7, NOTCH signaling Received: March 24, 2017 Accepted: August 08, 2017 Published: September 21, 2017 ABSTRACT Stem-like cells in tumor group featured the major role in the chemotherapy resistance of breast cancer, and the reduction of stem-like cells helped to perish the tumor when receiving chemotherapy. Smaller stem cells number indicated better therapeutic effect in vitro and in clinics, but how did miR-129 and Notch signaling function in breast cancer stem-like cells (BrCSCs) were unclear yet. Through using sphere forming assay and FACS sorting, we found that miR-129 decreased the proportion of stem-like cells in breast cancer cells. Results further indicated that miR-129 degraded the Estrogen Receptor 1 (ESR1) mRNA through a post-translational manner and contributed to the decline of stem-like cells number, preventing tumor regeneration. Cyclin d1 and DICER 1 were proved to promote Let-7 maturation, and in present study, we proved that miR-129 exhibited inhibition on ESR1 and halted the cyclin d1/DICER 1 sustaining of Let-7, which consequently released the Let-7 degradation of NUMB. The restoration of suppressive NUMB by upregulating miR-129 resulted in NOTCH signaling inhibition. In conclusion, we demonstrated the negative regulation of miR-129 on NOTCH signaling activation in BrCSCs’ renewal, which was achieved via continuous suppression on cyclin d1/DICER1 sustaining of Let-7 level, and eventually rescued the targeted inhibition of NUMB. The miR-129/ESR1 signaling played pivotal role in controlling DICER1/Let-7/NOTCH cascade via cyclin d1, revealing the novel mechanism of dual Let-7 in non-coding genes network.