Abstract
The role of microRNAs in small-cell lung carcinoma (SCLC) is largely unknown. miR-34a is known as a p53 regulated tumor suppressor microRNA in many cancer types. However, its therapeutic implication has never been studied in SCLC, a cancer type with frequent dysfunction of p53. We investigated the expression of a panel of 7 microRNAs (miR-21, miR-29b, miR-34a/b/c, miR-155, and let-7a) in 31 SCLC tumors, 14 SCLC cell lines, and 26 NSCLC cell lines. We observed significantly lower miR-21, miR-29b, and miR-34a expression in SCLC cell lines than in NSCLC cell lines. The expression of the 7 microRNAs was unrelated to SCLC patients' clinical characteristics and was neither prognostic in term of overall survival or progression-free survival nor predictive of treatment response. Overexpression or downregulation of miR-34a did not influence SCLC cell viability. The expression of these 7 microRNAs also did not predict in vitro sensitivity to cisplatin or etoposide in SCLC cell lines. Overexpression or downregulation of miR-34a did not influence sensitivity to cisplatin or etoposide in SCLC cell lines. In contrast to downregulation of the miR-34a target genes cMET and Axl by overexpression of miR-34a in NSCLC cell lines, the intrinsic expression of cMET and Axl was low in SCLC cell lines and was not influenced by overexpression of miR-34a. Our results suggest that the expression of the 7 selected microRNAs are not prognostic in SCLC patients, and miR-34a is unrelated to the malignant behavior of SCLC cells and is unlikely to be a therapeutic target.
Highlights
Small cell lung cancer (SCLC) accounts for about 10–20% of lung cancer cases and is notorious for its aggressiveness and poor survival rate [1,2]
Lower expression of miR-21, miR-29b, and miR-34a was found in SCLC cell lines than in non-small cell lung cancer (NSCLC) cell lines (p,0.001 for all three microRNAs, Figure S1), which is in agreement with a previous report [20]
We showed the expression of 7 known cancer-associated microRNAs in SCLC tumors and cell lines as well as in NSCLC cell lines
Summary
Small cell lung cancer (SCLC) accounts for about 10–20% of lung cancer cases and is notorious for its aggressiveness and poor survival rate [1,2]. The roles of microRNAs in cancer biology and prognosis prediction in non-small cell lung cancer (NSCLC) have been widely studied. Increased miR-34a was associated with fewer relapses in a small retrospective study of resected NSCLC patients [11]. Overexpression of let-7a, possibly through suppression of the RAS oncogene [12], was shown to be related to increased overall survival in NSCLC patients [13], and was among the protective prognostic factors preventing recurrence in surgically resected NSCLC [14]. SCLC is characterized by frequent p53 dysfunction [16], the role of miR-34a, a p53 regulated tumor suppressor microRNA [8,17], has never been studied in SCLC
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