SMAD‑6, ‑7 and ‑9 are potential molecular biomarkers for the prognosis in human lung cancer

Abstract

SMADs, a family of proteins that function as signal transducers and transcriptional regulators to regulate various signaling pathways, including the transforming growth factor-β signaling pathway, are similar to the mothers against decapentaplegic family of genes and the sma gene family in Caenorhabditis elegans. SMADs generate context-dependent modulation by interacting with various sequence-specific transcription factors, such as E2F4/5, c-Fos, GATA3, YY1 and SRF, which have been found to serve a key role in lung carcinoma oncogenesis and progression. However, the prognostic values of the eight SMADs in lung cancer have not been fully understood. In the present study, the expression levels and survival data of SMADs in patients with lung carcinoma from the Oncomine, Gene Expression Profiling Interactive Analysis, Kaplan-Meier plotter and cBioPortal databases were downloaded and analyzed. It was found that the mRNA expression levels of SMAD-6,-7 and-9 were decreased in lung adenocarcinoma and squamous cell carcinoma compared with that in adjacent normal tissues, while there was no significant difference in SMADs 1-5. Survival analysis revealed that not only were low transcriptional levels of SMAD-6,-7 and-9 associated with low overall survival but they also had prognostic role for progression-free survival and post-progression survival (P<0.05) in patients with lung carcinoma. In conclusion, the present study demonstrated that SMAD-6,-7 and-9 are potential biomarkers for the prognosis of patients with lung carcinoma.

Prognostic Significance of TLR2, SMAD3 and Localization-dependent SATB1 in Stage I and II Non–Small-Cell Lung Cancer Patients

“…In the experimental studies on other tumor types, this paradoxical effect of TGFβ has been shown to be mediated through , for example, SMAD3. 61 On the other hand, our analyses based on TCGA have shown that the expression of SMAD3 mRNA was significantly negatively correlated with patient survival, which is in agreement with Niu et al 59,60 Pan et al 62 revealed that SMAD3 was a tumor suppressor for post-progression survival but an oncogene for progression-free survival. In turn, Zeng et al 63 showed that increased SMAD3 mRNA levels were not related to OS in NSCLC patients from the CBioPortal cohort.…”

Transforming Growth Factor-Beta (TGF-β) Signaling in Cancer-A Betrayal Within

“…In addition to L3 loop, a three finger-like structure in Smad seven provides additional support to bind to TGFβRI ( Miyazawa and Miyazono, 2017 ). The binding of SMAD7 and TGFβRI blocks SMAD2/3 which further prevents the formation of R-Smad/Co-Smad complex, thereby inhibiting core signalling pathway ( Pan et al, 2020 ). In a similar manner, BMP and activin membrane-bound inhibitor (BAMBI) forms BAMBI/SMAD7/TGFβRI complex which inhibits the activation of SMAD3 ( Hernandez et al, 2018 ).…”

Lung microRNAs Expression in Lung Cancer and COPD: A Preliminary Study

“…In addition, we found an in silico interaction between hsa-miR-33a-5p and genes such as SMAD7 and ZNF281. Considering that SMAD7 acts as a transcriptional regulator and ZNF281 is a tumor-suppressive long non-coding (lnc)RNA, an increase in hsa-miR-33a-5p could lead to the downregulation of these factors and consequently to a loss of tumor suppression capability [ 57 , 58 , 59 ]. Among cells contributing to pro-tumor microenvironments, macrophages, especially of the M2 phenotype, are key players due to their ability to infiltrate the tumor microenvironment, leading to cancer progression [ 60 ].…”