Lung cancer is the leading cause of cancer-related mortality and morbidity and it is one of the predominant life-threatening conditions among cancers. For 50 years both the morbidity and mortality rates from many countries have increased significantly [
1]. However, the exact cause underlying lung cancer is still unrevealed. Improvements in long term survival rate have been achieved by early diagnosis and combinations of chemo/radiotherapy and surgery. However, the recurrence rate is still high and five years survival for NSCLC patients remains as low as 15% [
2]. One main factor could be the resistant cancer cells after certain therapies.
For now, there is no medicine shown to be significantly effective and consistent to treat lung cancer. When feasible, surgical resection is still the single most effective and successful option especially for early-stage patients [
3-
5]. There are two main types of lung cancer, small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC accounts for around 84% of all the cases. NSCLC patients are more likely to be cured with surgery resection if discovered at an early stage [
6]. Radiotherapy, chemotherapy, immunotherapy and combined treatments would be chosen based on tumour stage and histologic type based on accurate diagnosis. Radiotherapy is the most important localised treatment across every clinical phase of NSCLC patients. However, the records of the past two decades shown that only 5-10% of patients survived 5 years after clinical therapy [
7]. Malissard et al. has shown that there is a tight correlation between recurrence and distant metastasis [
8], therefore recurrence is the main cause responsible for failed treatment and the occurrence of metastasis of NSCLC. The recurrence is frequently associated with stress-resistant cancer cells after therapies [
9]. A study focusing on 598 stage I NSCLC patients who underwent surgery resection illustrated around 27% of overall recurrence incidences [
10]. Our project aimed to understand the forming process of stress-resistant lung cancer cells after radiotherapy. In our experiment, two classic NSCLC cell lines A549 and H1299 were chosen. Survived cells with three week’s radiation were used as the cell model after radiotherapy for further experiments.
Autophagy is a catabolic process to breakdown and recycles dysfunctional cellular components such as organelles and proteins by isolating these selected components inside a double membrane-bound vesicle. This function is used as a survival mechanism by starving cells [
11,
12]. When it comes to cancer cells, it could maintain the metabolism of mitochondrial, improve cell proliferation and increase stress tolerance. All of these effects together would eventually contribute to the level of malignance. Additionally, it may interfere with chemotherapy and radiation-induced apoptosis through removal of damaged organelles [
13]. These evidences suggest the role autophagy might play in tumor development [
14]. It hints that inhibition of autophagy activity is the effective way to suppress the development of cancer. MicroRNA is a single-stranded small sequence of non-coding RNA molecule with length of 20–24 nucleotides which accounts for post-transcriptional regulation of gene expression [
15,
16]. MicroRNA could silence gene expression by specific binding through base pairing with complementary mRNA sequence followed by degradation of the target mRNA [
17]. Therefore it plays a crucial role in regulation of gene expression, cell cycling and developmental timing [
18]. It is estimated that miRNAs modulates over one-third of human genes and various biological pathways [
19]. Some studies illustrated degradation of miRNA might contribute to the developments of various diseases including cancer [
20]. The link established between autophagy and miRNA is the possible regulation function of miRNA upon autophagy [
20]. Dysfunctional miRNAs are frequently found in malignancies where they function as either oncogenes or tumor suppressors [
21]. MiRNA has been suggested to prevent the development of lung cancer by inhibiting some specific function proteins involved in autophagy pathway. So far some researches have pointed out the potential correlation between dysfunctions of miRNA-186, 143 [
22], 17–92 cluster [
23,
24] and the progress of lung cancer. In this report, we also found the reduced expression level of miRNA-191 in two types of NSCLC based on miRNA microarray techniques. However, the link between miRNA-191 and autophagy has not been reported in other studies. Taken together, we propose that the inhibition mechanism to lung cancer by miRNA-191 is conducted by targeting specific proteins of autophagy pathway, which eventually inhibit the growth and proliferation of lung cancer cells. The phenomenon could be helpful for therapy of lung cancer in the future.