Long non-coding RNA MAFG-AS1 promotes proliferation and metastasis of breast cancer by modulating STC2 pathway.

Breast cancer is the most common cancer worldwide. A number of studies proposed that long non-coding RNA plays an essential role in the regulation of invasion and metastasis of various forms of malignancy, including lung cancer, gastric cancer, and bladder cancer. In this study, a long non-coding RNA(LncRNA) MAFG-AS1 was explored in detail to understand the significance in the etiology of breast cancer. The results indicated that expression of LncRNA MAFG-AS1 in the breast cancer tissues was significantly higher than the adjacent normal breast tissues and elevated expression level of LncRNA MAFG-AS1 was correlated to the larger tumor size, negative expression of ER, PR and lymph node metastasis. The potency of breast cancer proliferation, invasion, and metastasis was inhibited in the absence of LncRNA MAFG-AS1. Mechanically, LncRNA MAFG-AS1 was mainly located in the cytoplasm. The downstream target gene of LncRNA MAFG-AS1 was STC2 which might promote cell proliferation and metastasis in breast cancer and this study provides a new potential therapeutic target for breast cancer.

Long intergenic non-coding RNA 00473 promotes proliferation and migration of gastric cancer via the miR-16-5p/CCND2 axis and by regulating AQP3.

Gastric cancer (GC) is one of the most common malignancies worldwide, but its molecular mechanisms remain unclear. Increasing evidence indicates that long non-coding RNAs (LncRNAs) play a pivotal role in various cancers recently. Our present study focused on exploring the function of long intergenic non-coding RNA 00473 (LINC00473) in GC. In this study, we found that LINC00473 expression was aberrantly increased in tumor tissues compared with the paired para-cancerous tissues. The expression of high LINC00473 in GC was notably correlated with a higher risk of lymphatic metastasis, a higher incidence of vascular cancer embolus, and advanced TNM stage. Further experiments showed that the overexpression of LINC00473 could promote the proliferation and metastasis of GC cells both in vitro and in vivo. The apoptosis of GC cells increased significantly by the decrease of LINC00473. Mechanistically, LINC00473 could sponge miR-16-5p in the cytoplasm and relieve its suppression of CCND2. Moreover, AQP3 was found to be a significant downstream target gene for LINC00473 through RNA transcriptome sequencing, as demonstrated by qRT-PCR and western blot. Overexpression of LINC00473 can partially reverse the effects of AQP3 decrease on GC proliferation and metastasis. LINC00473 regulated AQP3 expression through CREB was confirmed by western blot. Our research indicates that LINC00473/miR-16-5p/CCND2 axis plays a role in the proliferation of GC and modulates AQP3 to influence GC cell metastasis, making it a potential therapeutic target for GC.

PKD3 promotes metastasis and growth of oral squamous cell carcinoma through positive feedback regulation with PD-L1 and activation of ERK-STAT1/3-EMT signalling.

Oral squamous cell carcinoma (OSCC) has a high incidence of metastasis. Tumour immunotherapy targeting PD-L1 or PD-1 has been revolutionary; however, only a few patients with OSCC respond to this treatment. Therefore, it is essential to gain insights into the molecular mechanisms underlying the growth and metastasis of OSCC. In this study, we analysed the expression levels of protein kinase D3 (PKD3) and PD-L1 and their correlation with the expression of mesenchymal and epithelial markers. We found that the expression of PKD3 and PD-L1 in OSCC cells and tissues was significantly increased, which correlated positively with that of mesenchymal markers but negatively with that of epithelial markers. Silencing PKD3 significantly inhibited the growth, metastasis and invasion of OSCC cells, while its overexpression promoted these processes. Our further analyses revealed that there was positive feedback regulation between PKD3 and PD-L1, which could drive EMT of OSCC cells via the ERK/STAT1/3 pathway, thereby promoting tumour growth and metastasis. Furthermore, silencing PKD3 significantly inhibited the expression of PD-L1, and lymph node metastasis of OSCC was investigated with a mouse footpad xenograft model. Thus, our findings provide a theoretical basis for targeting PKD3 as an alternative method to block EMT for regulating PD-L1 expression and inhibiting OSCC growth and metastasis.

The long noncoding RNA TINCR promotes breast cancer cell proliferation and migration by regulating OAS1.

Breast cancer is the leading cause of cancer-related death in women around the world. It is urgently needed to identify genes associated with tumorigenesis and prognosis, as well as to elucidate the molecular mechanisms underlying the oncogenic process. Long noncoding RNAs (lncRNAs) are widely involved in the pathological and physiological processes of organisms and play an important role as oncogenes or tumor suppressor genes, affecting the development and progression of tumors. In this study, we focused on terminal differentiation-induced non-coding RNA (TINCR) (GeneID:257000) and explore its role in the pathogenesis of breast cancer. The results showed that TINCR was increased in breast cancer tissue, and high expression level of TINCR was associated with older age, larger tumor size, and advanced TNM stage. High level of TINCR can promote proliferation and metastasis of breast cancer cells, while downregulation of TINCR induces G1-G0 arrest and apoptosis. Mechanismly, TINCR can bind to staufen1 (STAU1) and then guide STAU1 (GeneID:6780) to bind to OAS1 mRNA (NM_016816.4) to mediate its stability. Thus low level of OAS1(GeneID:4938) can lead to cell proliferation and migration. This result elucidates a new mechanism for TINCR in breast cancer development and provides a survival indicator and potential therapeutic target for breast cancer patients.

[Expression Level of Protein Kinase D in Oral Squamous Cell Carcinoma with Diverse Differentiation].

OBJECTIVE: This study aimed to investigate the expression level of protein kinase D (PKD) in oral squamous cell carcinoma (OSCC) and its relationship with differentiation of OSCC. METHODS: Sample was collected from 10 healthy control subjects and 40 OSCC confirmed by histopathological diagnosis, and the immunohistochemical staining was adopted to detect the expression of PKDs in OSCC tissues. The proportion of stained cell and staining intensity were evaluated to get a score, which used to analyze the difference among PKD1, PKD2 and PKD3 in various differentiation OSCC tissues. The correlations between the staining score of PKDs and differentiation of OSCC were further analyzed. RESULTS: PKD1 and PKD3 were high expression in OSCC tissues. There were statistical significance among the staining score of PKD1, PKD2 and PKD3 in various differentiation OSCC tissues ( P<0.001). In addition, there was a significantly negative correlation between the staining score of PKD1 and PKD2 with the differentiation of OSCC ( r=-0.574, -0.341, P<0.001). CONCLUSION: In OSCC tissues with different degree of differentiation, there might be some differences among PKDs which play a major role. The expression of PKD1 and PKD2 was correlated with the differentiation of OSCC, the poor differentiation of OSCC, the higher expression of PKD1 and PKD2.

Long intergenic non-coding RNA 00324 promotes gastric cancer cell proliferation via binding with HuR and stabilizing FAM83B expression.

Substantial evidence shows that long non-coding RNAs (lncRNAs) participate in many biological mechanisms, and their dysregulation are also involved in the development and progression of cancers, including gastric cancer (GC). Long intergenic non-coding RNA 00324 (LINC00324), a 2115 bp ncRNA, is located on chromosome 17p13.1. The biological function and molecular mechanisms of LINC00324 in GC remains undiscovered. In this paper, we found that the expression level of LINC00324 was significantly upregulated in GC tissues compared with the corresponding normal tissues. The overexpression of LINC00324 was correlated with advanced TNM stage, larger tumor size, and lymph node metastasis as well as poor prognosis. Further experiments revealed that knockdown of LINC00324 could suppress the proliferation of GC cells. RNA transcriptome sequencing technology revealed that FAM83B may be a significant downstream target gene of LINC00324. LINC00324 could combine with the RNA-binding protein (RBP) human antigen R (HuR) and thus stabilize the expression of FAM83B. Moreover, rescue assays showed that the reduced FAM83B expression partially reversed the promotion of cell growth in GC induced by the overexpression of LINC00324. In conclusion, our study revealed that LINC00324 acted as an oncogene in tumorigenesis and progression, suggesting that it could be a new biomarker in diagnosis and prognosis of GC.

[Long-term follow-up on disc renarrowing after anterior lumbar interbody fusion with autogenous tricortical iliac crest graft].

OBJECTIVE: To have a retrospective review of the patients undergoing anterior lumbar interbody fusion (ALIF) with clinical and radiological assessment, and observe changing of graft after procedure and assess correlation between graft collapse and recurrence of radiculopathy. METHODS: Sixty-seven consecutive patients undergoing ALIF only at L(4 - 5) with autologous iliac crest graft for intervertebral disc prolapse were followed-up for an average of 14 (2.5 - 32) years. The effect of the fusion was examined by the existence of radiolucent lines and bony continuity on plain radiographs and tomographs, or mobility on flexion-extension radiographs. The disc height was also measured. Lower limb radiculopathy was assessed based on the symptom and examination. Paired samples t-test was used for statistical analysis. RESULTS: Sixty-four patients with successful fusion were analyzed (fusion rate: 96%). All measurements in this study were completed by the same author, and the measurement error of more than 2 mm was statistically significant. According to this, graft collapse occurred in 55 patients (86%) and 9 patients (14%) had no graft collapse. In these 55 cases, the original disc height was (12.1 +/- 2.9) mm, increased immediately after the surgery to (16.2 +/- 1.9) mm, however re-narrowed to (12.9 +/- 2.7) mm at the first observation of solid fusion (a mean of 9 months, ranging from 5 to 14 months), which was not significant different compared to the original. There was no significant change in disc height after solid fusion and the disc space at the final follow-up was (12.6 +/- 2.3) mm. There was no radiculopathy observed in 52 cases (95%) during the follow-up. CONCLUSION: Disc space re-narrowing was observed in most cases after single level ALIF of L(4 - 5), however it was rarely less than the initial and unlikely to result in recurrence of radiculopathy.