Pirfenidone suppressed triple-negative breast cancer metastasis by inhibiting the activity of the TGF-ß/SMAD pathway.

Among breast cancer patients, metastases are the leading cause of death. Despite decades of effort, little progress has been made to improve the treatment of breast cancer metastases, especially triple-negative breast cancer (TNBC). The extracellular matrix plays an important role in tumour growth and metastasis by causing its deposition, remodelling, and signalling. As we know, the process of fibrosis results in excessive amounts of extracellular matrix being deposited within the cells. So, it will be interesting to study if the use of anti-fibrotic drugs in combination with conventional chemotherapy drugs can produce synergistic antitumor effects. In this study, we assessed the efficacy of Pirfenidone (PFD), an FDA-approved medication for the treatment of idiopathic pulmonary fibrosis, on TNBC cells as well as its anti-tumour effects in xenograft tumour model. PFD inhibited in a dose-dependent manner breast cancer cell proliferation, migration, and invasion, while promoted their apoptosis in vitro. PFD also suppressed TGF-ß-induced activation of Smad signalling pathway and expression level of EMT-inducing transcription factors (e.g. SNAI2, TWIST1, ZEB1) as well as the mesenchymal genes such as VIMENTIN and N-Cadherin. On the contrary, the expression level of epithelial marker gene E-Cadherin was up-regulated in the presence of PFD. In vivo, PFD alone exerted a milder but significant anti-tumour effect than the chemotherapy drug nanoparticle albumin-bound paclitaxel (nab-PTX) did in the breast cancer xenograft mouse model. Interestingly, PFD synergistically boosted the cancer-killing effect of nab-PTX. Furthermore, Our data suggest that PFD suppressed breast cancer metastasis by inhibiting the activity of the TGFß/SMAD pathway.

Long non-coding RNA ROR recruits histone transmethylase MLL1 to up-regulate TIMP3 expression and promote breast cancer progression.

BACKGROUND: As a significant cause of cancer deaths worldwide, breast cancer continues to be a troublesome malignancy. Long non-coding RNAs (lncRNAs) have been implicated in the development of breast cancer. Abnormal methylation has been associated with unfavorable breast cancer prognosis. Herein, the current study aimed to elucidate the role of lncRNA ROR in breast cancer. METHODS: RT-qPCR was performed to determine whether lncRNA ROR was highly expressed in breast cancer tissues, while lncRNA ROR expression was detected in both the nuclear and cytoplasm of breast cancer cells. MCF-7 cells were subsequently introduced with oe-lncRNA ROR, sh-lncRNA ROR to explore the effects of lncRNA ROR on cell proliferation, invasion and apoptosis. RESULTS: RIP, RNA pull-down and ChIP assays provided evidence suggesting that lncRNA ROR recruited transmethylase MLL1 to promote H3K4 trimethylation that enhanced TIMP3 transcription. The rescue experiments demonstrated that lncRNA ROR knockdown could inhibit the progression of breast cancer via the downregulation of TIMP3. Finally, the in vivo experiment findings consistently highlighted the suppressive effects of lncRNA ROR silencing on tumor growth. CONCLUSION: Taken together, our study demonstrates that silencing of lncRNA ROR inhibits breast cancer progression via repression of transmethylase MLL1 and TIMP3, emphasizing the potential of lncRNA ROR as a novel target against breast cancer.

LINC-PINT suppresses breast cancer cell proliferation and migration via MEIS2/PPP3CC/NF-κB pathway by sponging miR-576-5p.

BACKGROUND: Breast cancer (BCa) is the most frequent malignant tumor in women. Long non-coding RNAs (lncRNAs) have been acknowledged to exert critical regulating functions in various cancers. Long intergenic non-protein coding RNA, p53 induced transcript (LINC-PINT) has been reported to be a chemosensitizer and a tumor suppressor in BCa. However, its downstream molecular mechanism contributing to its tumor-suppressing role remains to be explored in BCa. METHODS: LINC-PINT expression in BCa tissues and cells was measured using quantitative real-time polymerase chain reaction (RT-qPCR). The proliferation of transfected BCa cells was examined by counting kit-8 (CCK-8) and EdU assay. The migrating ability of indicate BCa cells was assessed by wound healing assays. Bioinformatics analysis and mechanism experiments such as RNA immunoprecipitation (RIP), RNA pull down assay, and luciferase reporter assay, were applied to demonstrate the downstream targets of LINC-PINT. RESULTS: LINC-PINT was downregulated in BCa tissues and cell lines. Overexpression of LINC-PINT suppressed BCa cell proliferation and migration. LINC-PINT could interact with miR-576-5p to upregulate Meis homeobox 2 (MEIS2) that positively regulated protein phosphatase 3 catalytic subunit gamma (PPP3CC) by inactivating the nuclear factor-κB (NF-κB) pathway. CONCLUSIONS: These findings elucidated the anti-tumor role of LINC-PINT in BCa via the miR-576-5p/MEIS2/PPP3CC/NF-κB axis, which suggested that LINC-PINT might serve as a potential therapeutic target for BCa.

Retrospective study for correlation analysis of nutritional status with osteoporosis, sarcopenia and cognitive impairment in elderly patients with coronary heart disease.

Coronary heart disease (CHD) is an abbreviation of coronary atherosclerotic heart disease, which remains challenging for diagnosis and treatment. Current study aims to explore the correlation between geriatric nutritional risk index (GNRI) and osteoporosis, sarcopenia, cognitive dysfunction in elderly patients with CHD, and to analyze the clinical diagnostic value of GNRI in the above complications. A total of 92 elderly patients with CHD treated in Suzhou Ninth People's Hospital from January 2020 to October 2023 were retrospectively collected as the experimental group, and 68 non-CHD subjects matched for sex and age in the same period of physical examination were randomly selected as the control group. Osteoporosis, sarcopenia and cognitive dysfunction were analyzed in all patients, and the correlation between GNRI and these indices in different populations was analyzed by Spearman's rank correlation. The diagnostic efficacy of GNRI in osteoporosis, sarcopenia, and cognitive impairment was analyzed by ROC curves. There was no significant difference in age, sex distribution, body mass index (BMI) and serum biological indexes between the elderly patients with CHD and the control group (all P > 0.05). Correlation analysis showed that GNRI level was positively correlated with bone mineral content (BMC), bone mineral density (BMD) T value and osteocalcin (OCN) (All r > 0, P < 0.05). In addition, GNRI levels were positively correlated with skeletal muscle mass (ASMI), grip strength and calf circumference (CC) (All r > 0, P < 0.05). However, there was no significant correlation between GNRI levels and cognitive dysfunction-related indicators (P > 0.05). In the elderly and elderly with CHD, the diagnostic AUC of GNRI was 0.875 and 0.862 in osteoporosis, and 0.912 and 0.932 in sarcopenia, respectively. The level of GNRI is significantly correlated with osteoporosis and sarcopenia. GNRI level, as an auxiliary diagnostic tool in elderly patients with CHD, exerts important clinical significance for early detection of the risk of complications, such as osteoporosis and sarcopenia.

KDM3B-ETF1 fusion gene downregulates LMO2 via the WNT/ß-catenin signaling pathway, promoting metastasis of invasive ductal carcinoma.

Breast cancer is the most common malignancy for women, with invasive ductal carcinoma being the largest subtype of breast cancers, accounting for 75-80% of cases. However, the underlying mechanism of invasive ductal carcinoma remains unclear. In this study, we investigate the possible effects KDM3B-ETF1 fusion gene has on breast cancer cell metastasis, invasion and its downstream signaling mediators as revealed from RNA sequence data analysis. As predicted, KDM3B-ETF1 expression was increased in breast cancer tissues and cells. Overexpression of KDM3B-ETF1 in cancer cell lines promoted the growth and invasion of breast cancer cells, while KDM3B-ETF1 knockdown showed the opposite effects on malignant cell growth and invasion both in vivo and in vitro as evidenced by cell counting kit-8, Transwell assay and tumor xenograft in nude mice. On the contrary, LIM Domain Only 2 (LMO2) expression was significantly reduced in breast cancer tissues and cells. According to chromatin immunoprecipitation and Western blot analysis, KDM3B-ETF1 targets LMO2 and reduced the expression of LMO2, leading to an increase in WNT/ß-catenin signaling pathway and thus promoting invasion. In conclusion, fusion gene KDM3B-ETF1 inhibits LMO2, activates the Wnt/ß-catenin signaling pathway that leads to increased breast cancer cell invasion and metastasis, providing a novel insight into developing therapeutic strategies. These results provide novel insights into the molecular mechanism of invasive ductal carcinomas, which may lead to potential therapeutic targets.

Analysis of the application of echocardiography technology in diagnosis of acute myocardial infection.

The purpose of this study is to enhance the diagnosis and treatment of acute myocardial infarction, prolong the life of patients with coronary heart disease, and improve the survival rate. In this study, 30 healthy adults are classified as the control group, and real-time three-dimensional echocardiography technology is used to observe the myocardial changes and characteristics of right ventricular morphology after acute myocardial infarction, which provides a theoretical basis for early clinical diagnosis and early intervention. The results show that the real-time three-dimensional echocardiography can provide more diagnostic information through the three-dimensional imaging of the cardiac structure and the real-time observation of the cardiac structures and their adjacent relations from any angle by combining the cutting and rotation of the image. Conventional examination methods such as two-dimensional echocardiography have a narrow time window for the detection of transient myocardial ischemia, which can clearly diagnose the ischemia in early stage, but its diagnostic ability in the late stage of ischemia is limited. When obtaining the cardiac full volume image within one cardiac cycle, echocardiography can quickly acquire dynamic images of ventricular volume without splicing and combine with the function of automatic delineation of endocardium of the 3d workstation to construct a real ventricular stereo image independent of the assumptions of the geometric model, so as to solve the inconvenience of the complex right ventricular space configuration and the obvious difference of its shape with the different load state. Therefore, as a new non-invasive imaging technique, it has unique advantages in accurate measurement of heart volume and evaluation of heart function.