TNNC1 Reduced Gemcitabine Sensitivity of Nonsmall-Cell Lung Cancer by Increasing Autophagy

Abstract

Background As we know, chemotherapy resistance is a critical factor leading to recurrence and metastasis of nonsmall-cell lung cancer (NSCLC). To clarify the key target and potential mechanism of resistance to gemcitabine (GEM) in NSCLC, we selected Gene Expression Omnibus Data Set and statistically analyzed a parent cell group and a GEM-resistant cell group. Results showed that the expression of troponin C1, slow skeletal and cardiac type (TNNC1) in GEM-resistant cells was higher than in parent cells, which implies that TNNC1 was associated with GEM resistance in lung cancer cells. Material/Methods TNNC1 expression level was detected by reverse transcription-quantitative polymerase chain reaction or western blot in GEM-resistant patient serum and cell lines. It could reduce or increase autophagy response and GEM resistance accordingly by inhibition of the short interfering ribonucleic acid or by forced overexpression of TNNC1 viruses in A549 cell line and GEM-resistant cell line (A549/GemR) respectively. Blocking autophagy with 3-methyladenine increased the sensitivity of chemotherapy confirmed by flow cytometry and microtubule-associated protein 1A/1B – light chain 3 punctate assay. What’s more, in a loss-of-function model, silencing of forkhead box 03 (FOXO3) in A549/GemR cells could rescue the autophagy weakened by TNNC1. Results TNNC1 promoted GEM chemoresistance of NSCLC by activating cytoprotective autophagy, regulated negatively by FOXO3. This research may provide a completely new strategy for NSCLC treatment. Conclusions Targeting the TNNC1/FOXO3 signaling pathway in NSCLC may be a novel strategy to combat GEM resistance.

Troponin C-1 Activated by E2F1 Accelerates Gastric Cancer Progression via Regulating TGF-β/Smad Signaling

“…Through cytoskeleton reorganization, overexpression of TNNC1 regulated epithelial cancer cell motility [30]. Besides, TNNC1 was reported as an oncogenic gene in non-small-cell lung cancer [31] and ovarian cancer [32]. In this study, we for the first time revealed the oncogenic role of TNNC1 in gastric cancer cells.…”

“…Besides, troponin genes were reported to be aberrant expressed in various cancer cells, and play roles as oncogenic or anti-tumor mediator [12]. For the selected examples, TNNC1 was found to be highly expressed in nonsmall-cell lung cancer cells and it was able to reduce chemotherapy resistance [31]. Inhibition of TNNC1 expression was effective in controlling the metastasis of ovarian cancer [32].…”

Sinigrin improves cerebral ischaemia‐reperfusion injury by inhibiting the TLR4 pathway‐mediated oxidative stress

“…(Sanches et al., 2019) Restoring blood flow through pharmacological or mechanical intervention is the key for treating ischaemic injury. (Ye et al., 2020) However, reperfusion can lead to severe secondary injury, known as, cerebral ischaemia‐reperfusion (CIR) injury. (Doyle et al., 2008) There is an urgent need to find more effective drugs to reduce brain injury and improve brain function in patients with CIR.…”

Study on potential differentially expressed genes in idiopathic pulmonary fibrosis by bioinformatics and next generation sequencing data analysis

“…CX3CR1 [441], S100A12 [442], PF4 [443], MPO (myeloperoxidase) [444], WNT7A [445], SLC6A4 [446], BDNF (brain derived neurotrophic factor) [447], CXCL10 [448], NEK7 [449], CYP1B1 [450], ABCA3 [451], TRIB3 [452], PCSK9 [453], FGF2 [454], ACKR4 [455], FASN (fatty acid synthase) [456], VIP (vasoactive intestinal peptide) [457], KL (klotho) [458], BMPR2 [459], APOA1 [323], TLR3 [460], CCR2 [461], TLR7 [462], CAV1 [463], WWC2 [464], TFPI (tissue factor pathway inhibitor) [465], EPAS1 [466] and CCDC40 [467] could serve as a potential therapeutic for pulmonary hypertension treatment. A previous study reported that the genes include CX3CR1 [468], CSF2 [469], CLDN18 [470], TRIM58 [471], PF4 [472], FFAR2 [473], MPO (myeloperoxidase) [474], CD5L [475], SH3GL2 [476], ITGA2B [477], S100A8 [478], VEGFD (vascular endothelial growth factor D) [479], CXCL11 [480], IL1A [481], WNT7A [482], SSTR1 [483], AQP4 [484], SCD (stearoyl-CoA desaturase) [485], SLC6A4 [486], BDNF (brain derived neurotrophic factor) [487], CXCL10 [488], ODAM (odontogenic, ameloblast associated) [489], CASP5 [490], CCL8 [491], TMEM100 [492], S100A9 [493], IL1B [494], CXCR1 [495], CXCR2 [496], WNT3A [497], BMI1 [498], CYP1B1 [499], FCN3 [500], TTN (titin) [501], SHISA3 [502], AZGP1 [503], ABCA3 [504], CD36 [505], EDNRB (endothelin receptor type B) [506], BTNL9 507], CEBPA (CCAAT enhancer binding protein alpha) [508], TRIB3 [509], TNNC1 [510], PCSK9 […”