Colorectal cancer (CRC) is one of the most frequent malignant tumors. Signaling by the PI3K/AKT pathway is crucial for CRC development and progression, including proliferation and migration. Celastrol has an anticancer effect, but its mechanism needs to be determined. Here, we showed that celastrol suppressed CRC cell proliferation and migration. Celastrol treatment also decreased the PI3K/AKT pathway components, and MMP3 and MMP7 expression levels. In addition, knockdown of AKT, not mTOR, inhibited MMP3 and MMP7 expression levels and AKT silencing promoted the celastrol-induced effects on CRC cell proliferation and migration. Taken together, these findings indicated that the celastrol-induced antitumor effects were mediated through MMP3 and MMP7 by the PI3K/AKT signaling pathway.

The aim of the current study is to investigate programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) expressions and to analyze the relationship between the expression of PD-L1 and PD-1 proteins and the molecular type, clinicopathological factors, and prognosis of invasive ductal carcinoma. We enrolled 136 patients with invasive ductal carcinoma of the breast. The expression of PD-L1 in tumor cells and that of PD-1 on paratumor-infiltrating immune cells was detected by immunohistochemistry, and the data were analyzed using SPSS software. The positive expression rates of PD-L1 and PD-1 in triple-negative breast cancer (TNBC) were 47.8 and 43.5%, which were higher than those of other subtypes (P<0.05). The expression of PD-L1 in tumor cells was correlated with the expression of estrogen receptor, progesterone receptor, and Ki-67 (P<0.05). The expression of PD-1 in the tumor-infiltrating immune cells was correlated with the expression of estrogen receptor, progesterone receptor, and Ki-67 and the histological grade (P<0.05). The expression of PD-L1 in tumor cells was correlated with the expression of PD-1 in paratumor-infiltrating immune cells (P<0.001). The expression of PD-L1 in tumor cells was found to be an independent prognostic risk factor with the progression-free survival rate for breast invasive ductal carcinoma (P=0.003). These results indicate that PD-L1 and PD-1 were highly expressed in TNBC which suggests that patients with TNBC may benefit from targeted immune therapies to a greater degree than patients with other subtypes. PD-L1 expression is an independent risk factor for breast invasive ductal carcinoma and expression of PD-L1 is expected to be a prognostic factor for breast cancer.

Intervertebral disc degeneration (IVDD) is a degenerative musculoskeletal disorder with multiple causative factors, such as age, genetics, mechanics and life style. IVDD contributes to non‑specific lower back pain (NLBP), which is a globally prevalent and debilitating musculoskeletal disorder. NLBP has a substantial impact on medical resources and creates an economic burden for the public. Dysregulated phenotypes of nucleus pulposus (NP) cells and endplate chondrocytes, such as proliferation, senescence and apoptosis, along with aberrant expression of extracellular matrix components, including type II collagen and aggrecan, are involved in the pathological process of IVDD. Evidence indicates that non‑coding RNAs, mainly microRNAs (miRNAs), long non‑coding RNAs (lncRNAs) and circular RNAs (circRNAs), play a vital role in the development of IVDD. In the present review, the potential molecular mechanisms of miRNAs, lncRNAs and circRNAs in the initiation and progression of IVDD were described based on the latest literature. Furthermore, ways to influence the functions of NP cells and endplate chondrocytes in IVDD were also summarized. The presented insights suggested that non‑coding RNAs may function as potential targets for the treatment of IVDD.

Background: When considering therapies for lung adenocarcinoma (LUAD) patients, the carcinogenic mechanisms of smokers are believed to differ from those who have never smoked. The rising trend in the proportion of nonsmokers in LUAD urgently requires the understanding of such differences at a molecular level for the development of precision medicine. Methods: Three independent LUAD tumor sample sets—TCGA, SPORE and EDRN—were used. Genome patterns of expression (GE), copy number variation (CNV) and methylation (ME) were reviewed to discover the differences between them for both smokers and nonsmokers. Tobacco-related signature genes distinguishing these two groups of LUAD were identified using the GE, ME and CNV values of the whole genome. To do this, a novel iterative multi-step selection method based on the partial least squares (PLS) algorithm was proposed to overcome the high variable dimension and high noise inherent in the data. This method can thoroughly evaluate the importance of genes according to their statistical differences, biological functions and contributions to the tobacco exposure classification model. The kernel partial least squares (KPLS) method was used to further optimize the accuracies of the classification models. Results: Forty-three, forty-eight and seventy-five genes were identified as GE, ME and CNV signatures, respectively, to distinguish smokers from nonsmokers. Using only the gene expression values of these 43 GE signature genes, ME values of the 48 ME signature genes or copy numbers of the 75 CNV signature genes, the accuracies of TCGA training and SPORE/EDRN independent validation datasets all exceed 76%. More importantly, the focal amplicon in Telomerase Reverse Transcriptase in nonsmokers, the broad deletion in ChrY in male nonsmokers and the greater amplification of MDM2 in female nonsmokers may explain why nonsmokers of both genders tend to suffer LUAD. These pattern analysis results may have clear biological interpretation in the molecular mechanism of tumorigenesis. Meanwhile, the identified signature genes may serve as potential drug targets for the precision medicine of LUAD.