The mismatch between bony endplates (BEPs) and grafted bone (GB) triggers several complications biomechanically. However, no published study has identified whether this factor increases the risk of screw loosening by deteriorating the local stress levels. This study aimed to illustrate the biomechanical effects of the mismatch between BEP and GB and the related risk of screw loosening. In this study, radiographic and demographic data of 56 patients treated by single segment oblique lumbar interbody fusion (OLIF) with anterior lateral single rod (ALSR) fixation were collected retrospectively, and the match sufficiency between BEP and GB was measured and presented as the grafted bony occupancy rate (GBOR). Data in patients with and without screw loosening were compared; regression analyses identified independent risk factors. OLIF with different GBORs was simulated in a previously constructed and validated lumbosacral model, and biomechanical indicators related to screw loosening were computed in surgical models. The radiographic review and numerical simulations showed that the coronal plane’s GBOR was significantly lower in screw loosening patients both in the cranial and caudal vertebral bodies; the decrease in the coronal plane’s GBOR has been proven to be an independent risk factor for screw loosening. In addition, numerical mechanical simulations showed that the poor match between BEP and GB will lead to stress concentration on both screws and bone-screw interfaces. Therefore, we can conclude that the mismatch between the BEP and GB will increase the risk of screw loosening by deteriorating local stress levels, and the increase in the GBOR by modifying the OLIF cage’s design may be an effective method to optimize the patient’s prognosis.

Purpose Tumor metastasis is the main cause of death from breast cancer patients and cell migration plays a critical role in cancer metastasis. Recent studies have shown long non-coding RNAs (lncRNAs) play an essential role in the initiation and progression of cancer. In the present study, the role of an LncRNA, Rho GTPase Activating Protein 5- Antisense 1 (ARHGAP5-AS1) in breast cancer was investigated. Methods RNA sequencing was performed to find out dysregulated LncRNAs in MDA-MB-231-LM2 cells. Transwell migration assays and F-actin staining were utilized to estimate cell migration ability. RNA pulldown assays and RNA immunoprecipitation were used to prove the interaction between ARHGAP5-AS1 and SMAD7. Western blot and immunofluorescence imaging were used to examine the protein levels. Dual luciferase reporter assays were performed to evaluate the activation of TGF-β signaling. Results We analyzed the RNA-seq data of MDA-MB-231 and its highly metastatic derivative MDA-MB-231-LM2 cell lines (referred to as LM2) and identified a novel lncRNA (NR_027263) named as ARHGAP5-AS1, which expression was significantly downregulated in LM2 cells. Further functional investigation showed ARHGAP5-AS1 could inhibit cell migration via suppression of stress fibers in breast cancer cell lines. Afterwards, SMAD7 was further identified to interact with ARHGAP5-AS1 by its PY motif and thus its ubiquitination and degradation was blocked due to reduced interaction with E3 ligase SMURF1 and SMURF2. Moreover, ARHGAP5-AS1 could inhibit TGF-β signaling pathway due to its inhibitory role on SMAD7. Conclusion ARHGAP5-AS1 inhibits breast cancer cell migration via stabilization of SMAD7 protein and could serve as a novel biomarker and a potential target for breast cancer in the future.

The adaptation of tumour cells to hypoxic microenvironment is one of the most significant characteristics of many malignant tumour diseases including hepatocarcinoma. Recently, long non-coding RNAs (lncRNAs) have been reported to play important roles in the various levels of gene regulation thus functioning in growth and survival of tumour cells. Here, new hypoxia-related lncRNAs in hepatocarcinoma cells were screened and validated by lncRNA chip-array as well as real-time RT-PCR. Among them, a hypoxia-activated lncRNA that we identified and termed Hypoxia-Activated BNIP3 Overlapping Noncoding RNA (HABON), was not only regulated by hypoxic-induced factor-1α (HIF-1α) but its expression increased significantly under hypoxia in tumour cells. We deciphered the biological characteristics of HABON including its cell localization, genomic location, as well as its full-length sequence, and proved HABON could promote growth, proliferation and clone-formation of hepatocarcinoma cells under hypoxia. Then, we revealed that HABON was transcriptionally activated by HIF-1α in hypoxic cells, furthermore, it could interact with HIF-1α and promote its protein degradation, thus affecting transcription of HIF-1α's target genes to exert its effects on cells. Besides, the elevated expression of HABON under hypoxia could promote the transcriptional activation of BNIP3 through HIF-1α, and increasing the expression level of BNIP3. This research provides a novel clue for the adaptive survival and growth mechanism of tumour under hypoxia, and gives a way to reveal the nature of tumour cells' resistance characteristics to harsh microenvironment.

Background: Tumor metastasis is the main cause of death from breast cancer patients and cell migration plays a critical role in metastasis. Recent studies have shown long non-coding RNAs (lncRNAs) play an essential role in the initiation and progression of cancer. In the present study, the role of a LncRNA, ARHGAP5-AS1 in breast cancer was investigated. Methods: Bioinformation was analyzed for the expression of ARHGAP5-AS1. qRT-PCR was conducted to verify the expression of ARHGAP5-AS1 in breast cancer specimens. Transwell migration assays and F-actin staining were utilized to estimate cell migration ability. RNA pulldown assays and RNA immunoprecipitation were used to prove the interaction between ARHGAP5-AS1 and SMAD7. Western blot and immunofluorescence imaging were used to examine the protein levels. Dual luciferase reporter assays were performed to evaluate the activation of TGF-β signaling.Results: Compared to MDA-MB-231 cells, the expression of LncRNA ARHGAP5-AS1(NR_027263) was significantly suppressed in its highly metastatic subtype MDA-MB-231-LM2 cells. Functional study showed ARHGAP5-AS1 could inhibit cell migration via suppression of stress fibers in breast cancer cell lines. Afterwards, SMAD7 was further identified to interact with ARHGAP5-AS1 by its PY motif and thus its ubiquitination and degradation was blocked due to reduced interaction with E3 ligase SMURF1 and SMURF2. Moreover, ARHGAP5-AS1 could inhibit TGF-β signaling pathway due to its inhibitory role on SMAD7. Conclusions: Overall, these findings demonstrate that ARHGAP5-AS1 inhibits breast cancer cell migration and could server as a novel biomarker for breast cancer metastasis and a potent target for the treatment in the future.