KCNQ1OT1 lncRNA affects the proliferation, apoptosis, and chemoresistance of small cell lung cancer cells via the JAK2/ STAT3 axis

Abstract

Background: Small cell lung cancer (SCLC) is a devastating and aggressive neuroendocrine carcinoma characterized by high cellular proliferation and early metastatic spread. Numerous studies have demonstrated that long noncoding RNAs (lncRNAs) can regulate tumor generation and development, including in SCLC.The current study aimed to assess the effect of the lncRNA, KCNQ1OT1, on the proliferation, apoptosis, and chemoresistance of SCLC and the potential underlying molecular mechanism.Methods: Matched chemo-resistant and sensitive cells were applied to RNA isolation and followed by expression profiling by microarray analysis and subsequent quantitative polymerase chain reaction (qPCR) validation. Cell viability and apoptosis were determined by Cell Counting Kit-8 and flow cytometry to examine the chemoresistance and apoptosis of KCNQ1OT1 knockdown with lentivirus-mediated RNA interference. Furthermore, cell proliferation was studied by colony formation, and invasion and migration were tested by Transwell cell invasion and wound-healing assays, respectively. A tumor xenograft model was established to determine the role of KCNQ1OT1 in tumor growth and chemoresistance in response to KCNQ1OT1 knockdown in vivo. Western blot analysis, qPCR, and immunohistochemistry were used to detect the levels of messenger RNA (mRNA) Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway-related markers.Results: Higher expression of KCNQ1OT1 was detected in SCLC chemo-resistant verso chemo-sensitive cells. Knockdown of KCNQ1OT1 inhibited SCLC cell viability and cloning ability, hindered cell migration and invasion, induced apoptosis in vitro, and suppressed tumor growth and chemoresistance in vivo, by activating the JAK2/STAT3 signaling pathway.Conclusions: This is the first study to indicate that lncRNA KCNQ1OT1 promotes cell proliferation and invasion, and prevents apoptosis of SCLC by activating the JAK2/STAT3 pathway.

KCNQ1OT1: An Oncogenic Long Noncoding RNA

“…In addition, KCNQ1OT1 has been reported to play a role in metabolic reprogramming in CRC. Chen et al demonstrated that KCNQ1OT1 modulates HCT116 and SW48 CRC cell proliferation in glucose metabolism reprogramming by stabilizing hexokinase 2 (HK2) [ 38 ]. Together, studies suggest that higher levels of KCNQ1OT1 in CRC patients could reduce the effectiveness of some chemotherapeutic regimens and may be useful as a predictive biomarker of drug response, a prognostic indicator, and an immune therapy target.…”

Identification of Novel Biomarkers for Predicting Prognosis and Immunotherapy Response in Head and Neck Squamous Cell Carcinoma Based on ceRNA Network and Immune Infiltration Analysis

“…A previous report indicated that KCNQ1OT1 was associated with cell proliferation, apoptosis, prognosis, invasion, and metastasis in various cancers [ 10 , 42 – 44 ]. Further, KCNQ1OT1 facilitated invasion and inhibited apoptosis in oral squamous cell carcinoma by regulating the miR-185-5p/Rab14 axis [ 45 ].…”

Oncogenic Role of Exosomal Circular and Long Noncoding RNAs in Gastrointestinal Cancers

“…For example, KCNQ1OT1 significantly increases migration and invasion in hepatocellular carcinomas and osteosarcomas [143,144]. In small cell lung cancer, the inhibition of KCNQ1OT1 induces apoptosis and sensitizes cells to etoposide by interrupting JAK/STAT signaling [145]. Additionally, KCNQ1OT1 expression is upmodulated in methotrexate-resistant colorectal cancer cells, and KCNQ1OT1 silencing re-sensitizes resistant cells to methotrexate through downregulating cAMP-response element binding protein (CREB) and CREB-binding protein (CBP) levels [146].…”