Asynchrony of primary tumor and mediastinal lymph nodes response after neoadjuvant immunotherapy plus chemotherapy in a patient with stage IIIA non-small-cell lung cancer: a case report.

With the rapid development of immunotherapy, the efficacy and feasibility of neoadjuvant immunotherapy for early resectable non-small-cell lung cancer (NSCLC) has been demonstrated. However, there are still difficulties and controversies in evaluating the efficacy of neoadjuvant immunotherapy. In our report, we described a 43-year-old female patient who was diagnosed with stage IIIA (cT1N2M0) pulmonary adenocarcinoma. After two cycles of neoadjuvant immunotherapy (sintilimab) combined with chemotherapy, according to imaging evaluation, the efficacy of the primary lesion was evaluated as stable disease and the mediastinal lymph nodes were evaluated as partial response. However, the postoperative pathological evaluation showed the primary lesion was pathological complete response and the mediastinal lymph nodes were major pathological response. This indicated that neoadjuvant chemo-immunotherapy was effective for both primary and mediastinal lymph nodes, but regression of the lesions was not synchronous. This study provided a complete process of neoadjuvant treatment, illustrating the effectiveness and safety of neoadjuvant chemo-immunotherapy to a certain extent. It is also suggested that the evaluation of neoadjuvant immunotherapy should be combined with imaging and pathology, and the primary tumor and lymph nodes should be evaluated, respectively.

Nfib promotes chondrocyte proliferation and inhibits differentiation by mildly regulating Sox9 and its downstream genes.

BACKGROUND: Chondrocyte proliferation and differentiation play pivotal roles in regulating cartilage formation, endochondral bone formation, and repair. Cartilage damage and underdevelopment may cause severe joint diseases. Various transcription factors regulate cartilage development. Nuclear factor 1 B (Nfib) is a transcription factor that plays a regulatory role in various organs. However, the effect and mechanism of Nfib on the proliferation and differentiation of chondrocytes in cartilage are still largely unknown. METHODS AND RESULTS: In the present study, we investigated the gene expression patterns in primary chondrocytes with Nfib overexpression or silencing by RNA sequencing (RNA-seq) technology. The results showed that Nfib overexpression significantly up-regulated genes that are related to chondrocyte proliferation and extracellular matrix (ECM) synthesis and significantly down-regulated genes related to chondrocyte differentiation and ECM degradation. However, with Nfib silencing, the genes involved in promoting chondrocyte differentiation were significantly up-regulated, whereas those involved in promoting chondrocyte proliferation were significantly down-regulated. Furthermore, quantitative real-time PCR (qRT-PCR), western blot, alcian blue staining and immunofluorescence staining assays further confirmed that Nfib potentially promotes chondrocyte proliferation and extracellular synthesis but inhibits differentiation. CONCLUSIONS: The molecular mechanism of Nfib in promoting chondrocyte proliferation and inhibiting differentiation was probably achieved by stimulating Sox9 and its downstream genes. Thus, this study adds new insights regarding the underlying molecular mechanism of transcriptional regulation in cartilage.

Interferon regulatory factor 6 correlates with the progression of non-small cell lung cancer and can be regulated by miR-320.

OBJECTIVES: The expression of interferon regulatory factor 6 (IRF6) has been reported in several cancer types, but its roles underlying the progression of lung cancer have not been detailedly investigated. METHODS: The pairs of lung cancer tissues and para-carcinoma tissues and The Cancer Genome Atlas database were collected to detect IRF6 expression. Cell counting kit-8, transwell and terminal-deoxynucleoitidyl transferase-mediated nick end labelling assays were used to evaluate cell proliferation, migration and apoptosis. KEY FINDINGS: A significant up-regulation of IRF6 in both lung adenocarcinoma and lung squamous cell carcinoma tissues compared with normal non-tumor tissues. Subsequently, Immunostaining also revealed that canceration of lung tissues predisposed to evoke IRF6 expression. In vitro experiments revealed the antitumour effects, including growth and migration inhibition, of IRF6 siRNA transfection. Considering miR-320 as an endogenous inhibitor to IRF6, miR-320 mimics transfection led to the inhibition of proliferation and migration of lung cancer cells. However, overexpressed IRF6 neutralized the antineoplastic activities of miR-320 in lung cancer cells. CONCLUSIONS: The miR-320/IRF6 signalling axis was implicated in pulmonary canceration. miR-320 as an endogenous inhibitor of IRF6 provided a novel therapeutic strategy for the treatment of lung cancer.

Long non-coding RNA LINC00525 promotes the non-small cell lung cancer progression by targeting miR-338-3p/IRS2 axis.

Long non-coding RNA LINC00525 has been reported to be upregulated in non-small cell lung cancer (NSCLC), however, its biological roles and underlying mechanism involved in modulation of NSCLC remain largely unclear. Real-time PCR were performed to determine the expression of LINC00525 and miR-338-3p in NSCLC tissues and cell lines. Cell proliferation was detected by Cell Counting Kit-8 (CCK-8) and colony-formation assays. Cell migration and invasion were determined by wound healing and transwell invasion assays, respectively. Luciferase reporter and RNA immunoprecipitation (RIP) assays were applied to detect the interactions between molecules. The protein expression was measured by Western blot. Xenograft tumor was established to determine the effect of LINC00525 on NSCLC growth in vivo. LINC00525 expression was significantly upregualted in NSCLC tissues and cell lines, and correlated with poor prognosis. LINC00525 depletion inhibited the proliferation, migration and invasion in NSCLC cell line A549 and SPC-A1 cells. In vivo study further confirmed that LINC00525 knockdown inhibited tumor growth in nude model. Mechanically, LINC00525 served as a molecular sponge for miR-338-3p, and modulated expression of endogenous miR-338-3p-targeted insulin receptor substrate 2(IRS2). These findings indicated that LINC00525 might be the potential target for NSCLC treatment.